[ CAS No. 60827-45-4 ] {[proInfo.proName]}

Name: 60827-45-4|(2S)-(+)-3-Chloropropane-1,2-diol|98%
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Quality Control of [ 60827-45-4 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 60827-45-4 ]

Product Details of [ 60827-45-4 ]

CAS No. :	60827-45-4	MDL No. :	MFCD00210270
Formula :	C₃H₇ClO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SSZWWUDQMAHNAQ-GSVOUGTGSA-N
M.W :	110.54	Pubchem ID :	148904
Synonyms :

Calculated chemistry of [ 60827-45-4 ]

Physicochemical Properties

Num. heavy atoms :	6
Num. arom. heavy atoms :	0
Fraction Csp3 :	1.0
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	2.0
Molar Refractivity :	23.65
TPSA :	40.46 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.32 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.17
Log Po/w (XLOGP3) :	-0.49
Log Po/w (WLOGP) :	-0.42
Log Po/w (MLOGP) :	-0.18
Log Po/w (SILICOS-IT) :	0.16
Consensus Log Po/w :	0.05

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-0.08
Solubility :	91.0 mg/ml ; 0.823 mol/l
Class :	Very soluble
Log S (Ali) :	0.11
Solubility :	142.0 mg/ml ; 1.28 mol/l
Class :	Highly soluble
Log S (SILICOS-IT) :	-0.14
Solubility :	79.7 mg/ml ; 0.721 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.32

Safety of [ 60827-45-4 ]

Signal Word:	Danger	Class:	8,6.1
Precautionary Statements:	P261-P270-P202-P201-P271-P264-P280-P308+P313-P361+P364-P332+P313-P301+P310+P330-P302+P352+P312-P304+P340+P312-P305+P351+P338+P310-P405-P501	UN#:	2922
Hazard Statements:	H300-H311-H332-H315-H318-H361	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 60827-45-4 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 60827-45-4 ]
Downstream synthetic route of [ 60827-45-4 ]

[ 60827-45-4 ] Synthesis Path-Upstream 1~5

1
[ 106-89-8 ]
[ 67843-74-7 ]
[ 57090-45-6 ]
[ 60827-45-4 ]

Yield	Reaction Conditions	Operation in experiment
26%	With Aspergillus niger epoxide hydrolases immobilized onto modified Eupergit^® C In aq. phosphate buffer; dimethyl sulfoxide at 25℃; for 3 h; Enzymatic reaction	General procedure: Asymmetric hydrolysis of (R/S)-SO, (R/S)-PO and (R/S)-ECH were examined in a batch type reactor (1.1 cm × 5 cm). To 1.5 mL of 100 mM phosphate buffer (pH = 7.0 for the free and EHIL; pH = 6.5 for EHIF and EHIE), 100 L of the free EH solution (1 mg mL−1) or 30 mg of each immobilized EH was loaded and the mixture kept at 25 °C for 2 min. The reaction was initiated by the addition 0.4 mL of each racemic epoxide solution (0.5 M in DMSO). A hundred microliters of aliquots withdrawn at different time intervals (15, 30,60, 90, 120, 180 and 240 min) were mixed with 400 L of diethylether and analyzed by a Shodex ORpak CDC–453 HQ chiral HPLC column (4.6 mm × 150 mm) according to Yildirim et al. [23]. The enantiomers of styrene oxide and their vicinal diols were detected at 220 nm. The enantiomers of propylene oxide, epichlorohydrin and their vicinal diols were detected using a refractive index detector (Shimadzu RID-10A). The optical configurations of remaining epoxides and formed diols were identified by comparing the retention time of these compounds with their optically active standard forms. The enantiomeric excess (ee) values of formed vicinal diol and remaining epoxide were calculated from the equations: ee_epoxide=([S-R]_epoxide)/([S+R]_epoxide) and ee_diol=([R-S]_diol)/([R+S]_diol) The enantiomeric ratio values (E) of free and immobilized EHs were calculated from the equation proposed by Chen et al. [27]. E=(V_max(R)/K_m(R))/(V_max(S)/K_m(S)) where V_max(R)and K_m(R) values are maximum velocity and Michealis–Menten constant of free and immobilized EH preparations toward (R)-enantiomer of epoxide and V_max(S) and K_m(S) are corresponding values toward (S)-enantiomer of epoxide.

Reference： [1] Tetrahedron Letters, 2005, vol. 46, # 13, p. 2263 - 2266
[2] Advanced Synthesis and Catalysis, 2006, vol. 348, # 18, p. 2619 - 2625
[3] Journal of the American Chemical Society, 2001, vol. 123, # 11, p. 2687 - 2688
[4] Synthetic Communications, 2006, vol. 36, # 16, p. 2371 - 2383
[5] Synthetic Communications, 2006, vol. 36, # 16, p. 2371 - 2383
[6] Journal of Organometallic Chemistry, 2006, vol. 691, # 9, p. 1862 - 1872
[7] Journal of the American Chemical Society, 2002, vol. 124, # 7, p. 1307 - 1315
[8] Journal of Organic Chemistry, 1998, vol. 63, # 20, p. 6776 - 6777
[9] Synthesis, 2007, # 4, p. 583 - 589
[10] Journal of Molecular Catalysis B: Enzymatic, 2013, vol. 88, p. 84 - 90
[11] Chemical Communications, 2003, # 9, p. 1100 - 1101
[12] Journal of the American Chemical Society, 2002, vol. 124, # 7, p. 1307 - 1315
[13] Journal of Catalysis, 2007, vol. 248, # 2, p. 204 - 212
[14] Synthetic Communications, 2008, vol. 38, # 8, p. 1236 - 1248
[15] Advanced Synthesis and Catalysis, 2010, vol. 352, # 1, p. 85 - 91

2
[ 106-89-8 ]
[ 67843-74-7 ]
[ 51594-55-9 ]
[ 57090-45-6 ]
[ 60827-45-4 ]

Reference： [1] Journal of Organic Chemistry, 2006, vol. 71, # 5, p. 1825 - 1836
[2] Chemical Communications, 2007, # 10, p. 1086 - 1088
[3] Advanced Synthesis and Catalysis, 2010, vol. 352, # 1, p. 85 - 91

3
[ 60827-45-4 ]
[ 107-06-2 ]
[ 98-59-9 ]
[ 113826-06-5 ]

Yield	Reaction Conditions	Operation in experiment
70%	With hydrogenchloride; N,N-dimethylamino-pyridine; potassium carbonate; triethylamine In water	Comparative Example 3 To a suspension of 37.5 g of potassium carbonate (0.27 mol) and 250 ml of 1,2-dichloroethane, was added dropwise at 24-28° C. 20 g of (S)-3-chloro-1,2-propanediol (0.18 mol) (optical purity: 98.9percent ee). After finishing the addition, the solution was stirred for 26 hours and cooled. To the reaction solution were added dropwise under stirring at 5-10° C. 20.1 g of triethylamine (0.2 mol) and 0.4 g of N,N-dimethylaminopyridine (0.0033 mol) and 34.5 g of p-toluenesulfonyl chloride (0.18 ml) in order. After finishing the addition the mixture was stirred for 3 hours and the resulting salt was dissolved by adding 150 ml of 3percent hydrochloric acid. The organic layer was washed with 150 ml of 1percent hydrochloric acid and 150 ml of water. The excess solvent was removed under vacuo. The chemical purity and optical purity at that time were 93.7percent, 96.6percent ee respectively. The residue was recrystallized from isopropyl alcohol/hexane=1/1 (V/V) to give 28.9 g of (S)-glycidyl tosylate (yield 70percent). Chemical purity: 98.3percent, optical purity: 97.5percent ee

Reference： [1] Patent: US5965753, 1999, A,

4
[ 60827-45-4 ]
[ 168828-81-7 ]
[ 168828-82-8 ]

Reference： [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 34, p. 7614 - 7620

5
[ 60827-45-4 ]
[ 288570-67-2 ]
[ 444335-16-4 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 23, p. 4213 - 4216
[2] Patent: US2003/13737, 2003, A1,

[ 60827-45-4 ] Synthesis Path-Downstream 1~88

1
1-O-β-D-glucosyl-(2S)-3-chloropropylene glycol [ No CAS ]
[ 60827-45-4 ]

Reference： [1]Chemical and pharmaceutical bulletin,1985,vol. 33,p. 5547 - 5550

2
barium D-3-chloropropane-1,2-diol-1-phosphate [ No CAS ]
[ 57090-45-6 ]
[ 60827-45-4 ]

Reference： [1]Journal of the American Chemical Society,1985,vol. 107,p. 7019 - 7027

3
barium D-3-chloropropane-1,2-diol-1-phosphate [ No CAS ]
[ 60827-45-4 ]

Reference： [1]Journal of the American Chemical Society,1985,vol. 107,p. 7019 - 7027

4
[ 96-24-2 ]
[ 57090-45-6 ]
[ 60827-45-4 ]
D-3-chloropropane-1,2-diol-1-phosphate [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1985,vol. 107,p. 7019 - 7027

5
[ 96-24-2 ]
[ 60827-45-4 ]

Reference： [1]Tetrahedron Asymmetry,1994,vol. 5,p. 239 - 246

6
[ 78692-88-3 ]
[ 60827-45-4 ]

Reference： [1]Tetrahedron Asymmetry,1993,vol. 4,p. 2211 - 2218

7
[ 110-87-2 ]
[ 60827-45-4 ]
(S)-1-Chloro-3-(tetrahydro-pyran-2-yloxy)-propan-2-ol [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2005,p. 4891 - 4896

8
[ 60827-45-4 ]
[ 108-24-7 ]
acetic acid-3-chloro-(S)-2-hydroxy-propyl ester [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2005,p. 2782 - 2787

9
[ 60827-45-4 ]
[ 90-05-1 ]
[ 61248-76-8 ]

Reference： [1]Tetrahedron Asymmetry,2007,vol. 18,p. 1964 - 1970
[2]Journal of Medicinal Chemistry,2013,vol. 56,p. 5071 - 5078
[3]Tetrahedron Asymmetry,2006,vol. 17,p. 3015 - 3020

10
[ 1011475-45-8 ]
[ 60827-45-4 ]
(S)-3-{4-[5-(5,6-diethyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; isopropyl alcohol; at 60℃; for 72h;	Example 14 To a solution of 4-[5-(5,6-diethyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenol (100 mg, 0.296 mmol) in isopropanol (10 mL) and 3 N aq. NaOH (3 mL), (S)-3-chloro-1,2-propanediol (98 mg, 0.89 mmol) is added. The mixture is stirred at 60 C. for 24 h before another portion of (S)-3-chloro-1,2-propanediol (98 mg, 0.89 mmol) is added. Stirring is continued at 60 C. for 2 days. The mixture is diluted with EA and washed with sat. aq. NaHCO3 solution. The org. extract is dried over MgSO4, filtered and evaporated. The crude product is purified by chromatography on prep. TLC plates with EA-heptane to give (S)-3-{4-[5-(5,6-diethyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol (14 mg) as a red oil; LC-MS: tR=0.93 min, [M+1]+=412.16.
	With sodium hydroxide; In water; isopropyl alcohol; at 60℃; for 72h;	To a solution of 4-[5-(5,6-diethyl-pyridin-3-yl)-[1 ,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenol (100 mg, 0.296 mmol) in isopropanol (10 ml.) and 3 N aq. NaOH (3 ml_), (S)-3-chloro-1 ,2- propanediol (98 mg, 0.89 mmol) is added. The mixture is stirred at 600C for 24 h before another portion of (S)-3-chloro-1 ,2-propanediol (98 mg, 0.89 mmol) is added. Stirring is continued at 600C for 2 days. The mixture is diluted with EA and washed with sat. aq. NaHCOs solution. The org. extract is dried over MgSO4, filtered and evaporated. The crude product is purified by chromatography on prep. TLC plates with EA-heptane to give (S)-3- {4-[5-(5,6-diethyl-pyridin-3-yl)-[1 ,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenoxy}-propane-1 ,2- diol (14 mg) as a red oil; LC-MS: tR = 0.93 min, [M+1]+ = 412.16.

Reference： [1]Patent: US2010/168005,2010,A1 .Location in patent: Page/Page column 23
[2]Patent: WO2008/29370,2008,A1 .Location in patent: Page/Page column 52; 53

11
[ 60827-45-4 ]
[ 767-00-0 ]
[ 148460-02-0 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1618 - 1626

12
[ 23010-10-8 ]
[ 60827-45-4 ]
(S)-3-(2-tert-butoxyphenoxy)-propane-1,2-diol [ No CAS ]
(R)-3-(2-tert-butoxyphenoxy)-propane-1,2-diol [ No CAS ]

Reference： [1]Tetrahedron Asymmetry,2007,vol. 18,p. 1964 - 1970

13
[ 94-71-3 ]
[ 60827-45-4 ]
[ 139004-02-7 ]

Reference： [1]Tetrahedron Asymmetry,2007,vol. 18,p. 1964 - 1970

14
[ 60827-45-4 ]
[ 6280-96-2 ]
(S)-3-(2-propoxyphenoxy)-propane-1,2-diol [ No CAS ]

Reference： [1]Tetrahedron Asymmetry,2007,vol. 18,p. 1964 - 1970

15
[ 4812-20-8 ]
[ 60827-45-4 ]
(S)-3-(2-isopropoxyphenoxy)-propane-1,2-diol [ No CAS ]

Reference： [1]Tetrahedron Asymmetry,2007,vol. 18,p. 1964 - 1970

16
[ 60827-45-4 ]
[ 288570-82-1 ]
[ 487041-52-1 ]

Reference： [1]Patent: EP1229033,2002,A2 .Location in patent: Example 14

17
[ 107-05-1 ]
[ 60827-45-4 ]

Yield	Reaction Conditions	Operation in experiment
66.8%	In Na4e(CN)610H2; water; ethyl acetate; toluene;	6.9 Controlled Potential Electrocatalytic ADH of allyl Chloride A divided glass H-cell as described in Example-6.1 which is been equipped with a platinum-on-titanium metal anode (5 cm2 and a nickel foil cathode is charged in the cathode compartment with 90 ML of saturated aqueous NaH₂O₄olution and in the anode compartment with Na₄e(CN)₆10H₂ (4.84 g, 10.0 mmol), K₂O₃13.8 g, 100 mmol) and t-BuOH (45 ML)/water (55 ML), the chiral ligand, PHAL-DHQD (292 mg. 0.375 mmol), OsO₄0.196 M in toluene, 0.128 ML, 0.025 mmol) and allyl chloride (3.83 g, 50 mmol). The mixture is electrolyzed at 0.4 V (vs ref. Ag/AgCl) at 15 C until about 9090 coulombs (19 hrs, ca. 94% conversion) of electricity is used. After stirring without electricity for one hour, the anode reaction mixture is transferred to a flask (250 ML) and saturated with NaCl. The reaction mixture is then quenched with 5 g of Na₂O3 and extracted with 3 x 50 ML of ethyl acetate. The combined organic solution is washed with 10 ML of 5% H3O4queous solution saturated with NaCl, 15 ML of saturated NaCl solution and dried over 5 g of anhydrous Na2O4 After filtration and removal of solvent under vacuum, (S)-3-chloro-1,2-propanediol is obtained as a pale yellow oil (3.48 g, 66.8% yield based on 94% conversion). The ee of the diol is 54.9% by HPLC analysis of the bis-acetate derivative of the diol on a Chiracell OD column). A sample of this product is analyzed, subsequently, to provide the following physical characteristics: [alpha] [25/D] = +4.43 (c = 2.1, MeOH); literature: EP 0286059 for R-isomer, [alpha] [25/D] = -6.9 (c = 2.0, H2); 1 NMR: (CDCl3 delta 3.6-4.2O); (m, 7H); IR (neat) 3357, 2946, 1432, 1303, 1102, 747 cm-1

Reference： [1]Patent: EP643781,1998,B1

19
[ 24423-98-1 ]
[ 60827-45-4 ]

Yield	Reaction Conditions	Operation in experiment
	With Serratia-derived glycerol dehydrogenase; NADH; at 30℃; for 2h;pH 6.5;Aqueous phophate buffer; Enzymatic reaction;	(Example 9) Method for synthesizing (S)-3-chloro-1,2-propanediol A Serratia-derived glycerol dehydrogenase solution was obtained from a culture broth of Serratia marcescens IFO12648 strains by a purification operation comprising ammonium sulfate fractionation and ion-exchange chromatography. 1 ml of a 0.1M phosphate buffer (PH 6.5) containing 10 mul of the thus-obtained glycerol dehydrogenase solution, 1.5 mg of 1-chloro-3-hydroxyacetone, and 10 mg of NADH was stirred at 30C for 2 hours.. After the reaction was completed, the reaction solution was saturated with ammonium sulfate, and extracted with an equivalent volume of ethyl acetate.. The amounts of the substrate and product in the extract were measured by gas chromatography (GC) analysis to determine the conversion rate (%).. Also, the optical purity (%ee) of the product was measured by high-performance liquid chromatography (HPLC) analysis after the primary hydroxyl group of the product was tosylated with tosyl chloride.. As a result, (S)-3-chloro-1,2-propanediol was produced with a conversion rate of 100% and an optical purity of 100%ee..
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.

	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With D-glucose; NAD; In water;pH 7.0;Microbiological reaction;	(Example 12) Method for synthesizing (S)-3-chloro-1,2-propanediol Recombinant Escherichia coli HB101 (PNTSGG1) Accession No. FERM P-18449 were inoculated into 50 ml of sterilized 2*YT medium (16 g of tryptone, 10 g of yeast extract, 5 g of sodium chloride, and 1L of water, PH 7.0 before sterillization) in a 500 ml Sakaguchi flask, and cultured with shaking at 37C for 18 hours.. Then, 10 mg of 1-chloro-3-hydroxyacetone, 0.6 mg of NAD+, and 25 mg of glucose were added to 1 ml of the resultant culture broth, and the mixture was then stirred at 30C for 2 hours.. After the reaction was completed, the conversion rate and optical purity of the reaction product (S)-3-chloro-1,2-propanediol were analyzed by the same method as in Example 9.. As a result, the conversion rate was 97.1%, and the optical purity was 100%ee.
	With Cellulomonas-derived glycerol dehydrogenase; NADH;Enzymatic reaction;	(Example 10) Method for synthesizing (S)-3-chloro-1,2-propanediol 1 ml of a 0.1M phosphate buffer (PH 6.5) containing 0.05 mg of Cellulomonas-derived glycerol dehydrogenase (produced by SIGMA), 1.5 mg of 1-chloro-3-hydroxyacetone, and 10 mg of NADH was stirred at 30C for 2 hours.. After the reaction was completed, the conversion rate and optical purity of the reaction product (S)-3-chloro-1,2-propanediol were analyzed by the same method as in Example 9.. As a result, the conversion rate was 100%, and the optical purity was 99.7%ee.

Reference： [1]Patent: EP1422213,2004,A1 .Location in patent: Page 18
[2]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[3]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[4]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[5]Patent: EP1422213,2004,A1 .Location in patent: Page 18
[6]Patent: EP1422213,2004,A1 .Location in patent: Page 18

20
[ 24423-98-1 ]
[ 57090-45-6 ]
[ 60827-45-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.

	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With potassium dihydrogenphosphate; D-glucose; In water; at 30℃; for 24h;pH 5.5;Aqueous phophate buffer; Microbiological reaction;	(Example 1) A liquid medium (pH 7.0) containing 4% of glucose, 0.3% of yeast extract, 1.3% of KH2PO4, 0.7% of (NH4)2HPO4, 0.01% of NaCl, 0.08% of MgSO4·7H2O, 0.006% of ZnSO4·7H2O, 0.009% of FeSO4·7H2O, 0.0005% of CuSO4·5H2O, and 0.001% of MnSO4·4-5H2O was prepared, and 5 ml of the liquid medium was injected into each of large test tubes and then sterilized with steam at 120C for 20 minutes. Then, one platinum loop of the microorganisms of each of the genera shown in Table 1 and 2 was inoculated into the liquid medium, and cultured with shaking at 30C for 2 to 3 days. Cells were collected from each of the culture broths by centrifugation, washed with water and then suspended in 1 ml of a 0.1M phosphate buffer (pH 5.5). Then, 0.5 ml of the cell suspension was mixed with 0.5 ml of a 0.1M KH2PO4 aqueous solution containing 5 mg of 1-chloro-3-hydroxyacetone and 20 mg of glucose, and the resultant mixture was placed in a test tube with a stopper and shaken at 30C for 24 hours. After completion of reaction, a saturated amount of ammonium sulfate was added to the reaction solution, and extraction was performed with an equivalent volume of ethyl acetate.
	With D-glucose; NAD; In water; at 30℃; for 2h;Microbiological reaction;	5(Example 13) Method for synthesizing (S)-3-chloro1,2-propanediol[0091] Recombinant Escherichia coli HB101 (pNTCRG) Accession No. FERM BP-6898 were inoculated into 50 mlof sterilized 23YT medium (16 g of tryptone, 10 g of yeast extract, 5 g of sodium chloride, and 1L of water, pH 7.0before sterillization) in a 500 ml Sakaguchi flask, and cultured with shaking at 37C for 18 hours. Then, 10 mg of1-chloro-3-hydroxyacetone, 70 mg of NAD+, and 25 mg of glucose were added to 1 ml of the resultant culture broth,and the mixture was then stirred at 30C for 2 hours. After the reaction was completed, the conversion rate and opticalpurity of the reaction product (S)-3-chloro-1,2-propanediol were analyzed by the same method as in Example 9. As aresult, the conversion rate was 42.8%, and the optical purity was 45.8%ee.

Reference： [1]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[2]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[3]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[4]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[5]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[6]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[7]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[8]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[9]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[10]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[11]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[12]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[13]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[14]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[15]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[16]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[17]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[18]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[19]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[20]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[21]Patent: EP1422213,2004,A1 .Location in patent: Page 13
[22]Patent: EP1422213,2004,A1 .Location in patent: Page 19

21
[ 67843-74-7 ]
[ 60827-45-4 ]

Yield	Reaction Conditions	Operation in experiment
95.4%Chromat.		Example 1 Preparation of (S)-3-chloro-1,2-propanediol To a mixture of N',N'-bis(3,5-di-tertbutylsalicylidene) ethylenediaminatocobalt(II) (119 mg, 0.216 mmol) and tetrahydrofuran (THF) (2.0 ml) was added (+) camphorsulfonic acid (60.3 mg, 0.260 mmol) and the reaction system was stirred for 1 hour while being filled with air.Thereto, namely to cobalt (III) complex in THF solution was added (S)-epichlorohydrin (1.00 g, 10.8 mmol, optical purity 99% e.e.) and water (234 mul, 13.0 mmol) in order, and the mixture was stirred for 20 hours at room temperature.After the reaction, quantitative analysis and optical purity measurement were conducted by gas chromatography on the reaction solution.As a result the subject compound, (S)-3-chloro-1,2-propanediol. (1.14 g, 95.4%) was produced with optical purity at 99% e.e.

Reference： [1]Patent: US2004/24254,2004,A1 .Location in patent: Page 4

22
[ 60827-45-4 ]
[ 82079-44-5 ]

Reference： [1]Patent: WO2004/65369,2004,A1 .Location in patent: Page/Page column 34-35

23
[ 875012-84-3 ]
[ 60827-45-4 ]
(1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid 4-((S)-2,3-dihydroxy-propoxy)-3,5-dimethyl-benzylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; sodium iodide; In water; isopropyl alcohol; at 90℃; for 8h;	c) To a solution of (1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid 4-hydroxy-3,5-dimethyl-benzyIamide (8.9 mg, 0.025 mmol) in isopropanol (1 ml_) is added 2 N aq. NaOH (100 jaL), Nal (1 mg, 0.007 mmol) and (S)-3-chloro-propane-1,2-diol (11.1 mg, 0.1 mmol). The reaction mixture is heated to 90C and shaken for 8 h before it is cooled to it Formic acid (0.2 ml) is added and the reaction mixture is separated by prep. HPLC to give (1 aS,5aR)-1,1,2-trimethyl-1,1 a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid 4-((S)-2,3-dihydroxy-propoxy)-3,5-dimethyl-benzylamide (3.7 mg) as a colourless lyophilisate. LC-MS: tR = 0.94 min, [M+1]+ = 430.27.
	With sodium hydroxide;sodium iodide; In isopropyl alcohol; at 90℃; for 8h;	To a solution of (1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid 4-hydroxy-3,5-dimethyl-benzylamide (8.9mg, 0.025 mmol) in isopropanol (1 ml) is added 2 N aq. NaOH (100 pi), Nal (1mg, 0.007 mmol) and (S)-3-chloro-propane-1,2-diol (11.1 mg, 0.1 mmol). Thereaction mixture is heated to 90C and shaken for 8 h before it is cooled to rt.Formic acid (0.2 mL) is added and the reaction mixture is separated by prep.HPLC to give (1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid 4-((S)-2,3-dihydroxy-propoxy)-3,5-dimethyl-benzylamide (3.7 mg) as a colourless lyophilisate. LC-MS: tR = 0.94 min,[M+1]+ = 430.27.

Reference： [1]Patent: WO2006/10379,2006,A1 .Location in patent: Page/Page column 37
[2]Patent: WO2006/10544,2006,A2 .Location in patent: Page/Page column 41

24
[ 288-32-4 ]
[ 994-30-9 ]
[ 60827-45-4 ]
[ 352308-28-2 ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide;	a (2R)-3-Azido-1,2-bis(triethylsilyloxy)propane (2S)-3-Chloro-1,2-propanediol (3.30 g) was dissolved in 15 ml of DMF. Sodium azide (2.33 g) was added to the solution. The mixture was stirred at 100 C. for 20 hr. DMF (15 ml) was added to the reaction solution. Imidazole (2.03 g) and 5.67 ml of triethylsilyl chloride were added thereto under cooling in ice. The mixture was stirred for 10 min. Imidazole (2.23 g) and 5.95 ml of triethylsilyl chloride were added thereto. The mixture was stirred for 10 min. Brine (120 ml) was then added to the reaction solution, and the mixture was extracted with 120 ml of diethyl ether three times. The combined organic layers were dried over anhydrous magnesium sulfate, and were filtered. The solvent was removed by distillation under the reduced pressure. Thus, 11.21 g of (2R)-3-azido-1,2-bis(triethylsilyloxy)propane was prepared. NMR (CDCl3) delta: 0.57-0.67 (18H, m), 0.91-1.01 (12H, m), 3.19-3.43 (2H, m), 3.49-3.61 (2H, m), 3.80-3.87 (1H, m)

Reference： [1]Patent: US2003/22881,2003,A1

25
(S,S)-Co(salen) [ No CAS ]
[ 107-98-2 ]
[ 106-89-8 ]
[ 62-23-7 ]
[ 60827-45-4 ]

Yield	Reaction Conditions	Operation in experiment
99%	In water;	EXAMPLE 5 Preparation of (S)-3-Chloro-1,2-propanediol with (S,S)-Co(salen): To a 3-necked, 250-mL, round-bottomed flask fitted with a vacuum adapter, an air inlet, and a temperature probe was added (S,S)-Co(salen) (1.51 g, 0.0023 mol, 0.23 mol %), propylene glycol monomethyl ether (20 mL), and p-nitrobenzoic acid (0.835 g, 0.0049 mol, 0.49 mol %). A slight vacuum was applied to pull air into the reaction medium, and the reaction was allowed to stir for 1 h. The air inlet was removed, and epichlorohydrin (92.52 g, 78.40 mL, 1.00 mol) was charged after the reaction vessel was purged with nitrogen. The reaction was cooled to 0 C., and water (8.1 g, 8.1 mL, 0.45 mol, 45 mol %) was slowly added, maintaining the reaction temperature below 5 C. The reaction was allowed to stir at room temperature for 16 h. When determined to be complete, the reaction was partitioned between toluene (80 mL) and water (80 mL). The aqueous layer was collected and washed with toluene (80 mL) to remove unreacted epichlorohydrin (isopropyl alcohol (20%) was added to facilitate the phase separation). After concentration of aqueous layer, the residue was vacuum distilled to give (S)-3-chloro-1,2-propanediol (37.4 g, 76% yield, >99% purity, 97% ee; b.p. 115-120 C. a 10 mm Hg).

Reference： [1]Patent: US2003/73855,2003,A1

26
[ 60827-45-4 ]
[ 107-06-2 ]
[ 98-59-9 ]
[ 113826-06-5 ]

Yield	Reaction Conditions	Operation in experiment
70%	With hydrogenchloride; N,N-dimethylamino-pyridine; potassium carbonate; triethylamine; In water;	Comparative Example 3 To a suspension of 37.5 g of potassium carbonate (0.27 mol) and 250 ml of 1,2-dichloroethane, was added dropwise at 24-28 C. 20 g of (S)-3-chloro-1,2-propanediol (0.18 mol) (optical purity: 98.9% ee). After finishing the addition, the solution was stirred for 26 hours and cooled. To the reaction solution were added dropwise under stirring at 5-10 C. 20.1 g of triethylamine (0.2 mol) and 0.4 g of N,N-dimethylaminopyridine (0.0033 mol) and 34.5 g of p-toluenesulfonyl chloride (0.18 ml) in order. After finishing the addition the mixture was stirred for 3 hours and the resulting salt was dissolved by adding 150 ml of 3% hydrochloric acid. The organic layer was washed with 150 ml of 1% hydrochloric acid and 150 ml of water. The excess solvent was removed under vacuo. The chemical purity and optical purity at that time were 93.7%, 96.6% ee respectively. The residue was recrystallized from isopropyl alcohol/hexane=1/1 (V/V) to give 28.9 g of (S)-glycidyl tosylate (yield 70%). Chemical purity: 98.3%, optical purity: 97.5% ee

Reference： [1]Patent: US5965753,1999,A

27
[ 917873-20-2 ]
[ 60827-45-4 ]
3-[4-((S)-2,3-dihydroxy-propoxy)-3,5-dimethyl-phenyl]-1-(4-phenyl-5-trifluoro-methyl-thiophen-2-yl)-propan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; isopropyl alcohol; at 65℃; for 24h;	Example 2; A solution of 3-(4-hydroxy-3,5-dimethyl-phenyl)-1 -(4-phenyl-5-trifluoromethyl- thiophen-2-yl)-propan-1 -one (8 mg, 20 mumol) in 2-propanol (0.7 mL) and 2 N aq. NaOH (0.27 mL) is treated with (S)-3-chloro-propane-1 ,2-diol (9 mg, 80 mumol) and the mixture is stirred at 65 C for 24 h. The mixture is cooled to rt, diluted with formic EPO <DP n="22"/>acid (0.25 ml_) and separated by prep. HPLC (Waters Xterra MS18 19x50mm 5mum, 10 to 95% acetonitrile in water containing 0.5 % formic acid) to give 3-[4-((S)-2,3- dihydroxy-propoxy)-3,5-dimethyl-phenyl]-1 -(4-phenyl-5-trifluoro-methyl-thiophen-2- yl)-propan-1 -one (3 mg) as a colourless lyophilisate; LC-MS: tR = 1.06 min, [M+1]+ = 479.21.

Reference： [1]Patent: WO2006/137019,2006,A1 .Location in patent: Page/Page column 20-21

28
[ 917873-23-5 ]
[ 60827-45-4 ]
3-[4-((S)-2,3-dihydroxy-propoxy)-3,5-dimethyl-phenyl]-1-(5-methyl-4-phenyl-thiophen-2-yl)-propan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; isopropyl alcohol; at 70℃; for 24h;	Example 5; A solution of 3-(4-hydroxy-3,5-dimethyl-phenyl)-1 -(5-methyl-4-phenyl-thiophen-2-yl)- propan-1 -one (60 mg, 0.172 mmol) in 2-propanol (1 ml_) and 3 N aq. NaOH (0.3 ml_) is treated with (S)-3-chloro-propane-1 ,2-diol (95 mg, 0.86 mmol) and the mixture is stirred at 70C for 24 h. The solvent is evaporated and the residue is purified on prep. TLC plates with EA to give 3-[4-((S)-2,3-dihydroxy-propoxy)-3,5-dimethyl- phenyl]-1 -(5-methyl-4-phenyl-thiophen-2-yl)-propan-1 -one (44 mg) as an oil; LC-MS: tR = 1.00 min, [M+I]+ = 425.23; 1H NMR (CDCI3): delta 7.60 (s, 1 H), 7.46-7.32 (m, 5H), 6.88 (s, 2H), 4.1 1 -4.06 (m, 1 H), 3.86-3.80 (m, 4H), 3.19-3.1 1 (m, 2H), 2.98-2.91 (m, 2H), 2.72 (d, J = 5.3 Hz, 1 H), 2.53 (s, 3H), 2.25 (s, 6H), 2.1 1 -2.05 (m, 1 H).

Reference： [1]Patent: WO2006/137019,2006,A1 .Location in patent: Page/Page column 23

29
[ 917873-30-4 ]
[ 60827-45-4 ]
3-[4-((S)-2,3-dihydroxy-propoxy)-3,5-dimethyl-phenyl]-1-(5-ethyl-4-phenyl-thiophen-2-yl)-propan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; isopropyl alcohol; at 70℃; for 15h;	Example 10; A solution of 3-(4-hydroxy-3,5-dimethyl-phenyl)-1 -(5-ethyl-4-phenyl-thiophen-2-yl)- propan-1 -one (52 mg, 0.143 mmol) in 2-propanol (1 mL) and 3 N aq. NaOH (0.3 mL) is treated with (S)-3-chloro-propane-1 ,2-diol (79 mg, 0.71 mmol) and the mixture is stirred at 70C for 15 h. The reaction mixture is diluted with water and extracted with DCM. The solvent of the organic extract is evaporated and the crude product is purified on prep. TLC plates with heptane:EA 1 :3 to give 3-[4-((S)-2,3-dihydroxy- EPO <DP n="28"/>propoxy)-3,5-dimethyl-phenyl]-1 -(5-ethyl-4-phenyl-thiophen-2-yl)-propan-1 -one (14 mg) as a colourless resin; LC-MS: tR = 1.03 min, [M+1 ]+ = 439.25; 1H NMR (CDCI3): delta 7.58 (s, 1 H), 7.45-7.30 (m, 5H), 6.88 (s, 2H), 4.1 1 -4.04 (m, 1 H), 3.87-3.80 (m, 4H), 3.67-3.60 (m, 2H), 3.60-3.56 (m, 1 H), 3.48-3.40 (m, 1 H), 3.20-3.10 (m, 2H), 2.98- 2.87 (m, 4H), 2.25 (s, 6H), 1.30 (t, J = 7.6 Hz, 3H).

Reference： [1]Patent: WO2006/137019,2006,A1 .Location in patent: Page/Page column 26-27

30
1-(5-ethyl-4-o-tolyl-thiophen-2-yl)-3-(4-hydroxy-3,5-dimethyl-phenyl)-propan-1-one [ No CAS ]
[ 60827-45-4 ]
3-[4-((S)-2,3-dihydroxy-propoxy)-3,5-dimethyl-phenyl]-1-(5-ethyl-4-o-tolyl-thiophen-2-yl)-propan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In ethanol; water; at 60℃; for 14h;	Example 20; EPO <DP n="36"/>A solution of 1 -(5-ethyl-4-p-tolyl-thiophen-2-yl)-3-(4-hydroxy-3,5-dimethyl-phenyl)- propan-1 -one (18 mg, 48 mumol) in ethanol (1.5 ml_) and 3 N aq. NaOH (0.3 ml_) is treated with (S)-3-chloro-propane-1 ,2-diol (30 mul_) and the mixture is stirred at 60C for 14 h. The solvent is removed in vacuo and the residue is separated on prep. TLC plates with heptane:EA 2:1 to give 3-[4-((S)-2,3-dihydroxy-propoxy)-3,5-dimethyl- phenyl]-1 -(5-ethyl-4-o-tolyl-thiophen-2-yl)-propan-1 -one (4 mg) as a colourless resin; LC-MS: tR = 1.04 min, [M+I ]+ = 453.28; 1H NMR (CDCI3): delta 7.45 (s, 1 H), 7.29-7.08 (m, 4H), 6.87 (s, 2H), 4.1 1 -4.04 (m, 1 H), 3.87-3.80 (m, 4H), 3.16-3.10 (m, 2H), 2.97- 2.90 (m, 2H), 2.64 (q, J = 7.6 Hz, 2H), 2.24 (s, 3H), 2.17 (s, 6H), 1.20 (t, J = 7.6 Hz, 3H).

Reference： [1]Patent: WO2006/137019,2006,A1 .Location in patent: Page/Page column 34-35

31
1-(5-ethyl-4-p-tolyl-thiophen-2-yl)-3-(4-hydroxy-3,5-dimethyl-phenyl)-propan-1-one [ No CAS ]
[ 60827-45-4 ]
3-[4-((S)-2,3-dihydroxy-propoxy)-3,5-dimethyl-phenyl]-1-(5-ethyl-4-p-tolyl-thiophen-2-yl)-propan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In ethanol; water; at 60℃; for 140h;	Example 22; A solution of 1 -(5-ethyl-4-p-tolyl-thiophen-2-yl)-3-(4-hydroxy-3,5-dimethyl-phenyl)- propan-1 -one (47 mg, 0.125 mmol) in ethanol (2 mL) and 3 N aq. NaOH (0.5 mL) is treated with (S)-3-chloro-propane-1 ,2-diol (90 muL) and the mixture is stirred at 60C for 20 h. Another portion of (S)-3-chloro-propane-1 ,2-diol (60 muL) is added and stirring is continued at 60C for 5 days. The reaction mixture is diluted with water and extracted with DCM. The solvent of the organic extract is evaporated and the crude product is purified on prep. TLC plates with heptane:EA 2:1 to give 3-[4-((S)- 2,3-dihydroxy-propoxy)-3,5-dimethyl-phenyl]-1 -(5-ethyl-4-p-tolyl-thiophen-2-yl)- propan-1 -one (6 mg) as a colourless resin; LC-MS: tR = 1.05 min, [M+1 ]+ = 453.25; 1H NMR (CDCI3): delta 7.56 (s, 1 H), 7.30-7.21 (m, 4H), 6.88 (s, 2H), 4.1 1 -4.05 (m, 1 H), 3.87-3.80 (m, 4H), 3.18-3.1 1 (m, 2H), 2.98-2.85 (m, 4H), 2.39 (s, 3H), 2.25 (s, 6H), 1.29 (t, J = 7.6 Hz, 3H).

Reference： [1]Patent: WO2006/137019,2006,A1 .Location in patent: Page/Page column 37

32
[ 917873-59-7 ]
[ 60827-45-4 ]
3-[4-((S)-2,3-dihydroxy-propoxy)-3,5-dimethyl-phenyl]-1-(4-phenyl-5-propyl-thiophen-2-yl)-propan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; isopropyl alcohol; at 70℃; for 38h;	Example 24; A solution of 3-(4-hydroxy-3,5-dimethyl-phenyl)-1 -(4-phenyl-5-propyl-thiophen-2-yl)- propan-1 -one (47 mg, 125 mumol) in isopropanol (2 ml_) and 3 N aq. NaOH (0.5 ml_) is treated with (S)-3-chloro-propane-1 ,2-diol (55 mg, 0.50 mmol) and the mixture is stirred at 70C for 14 h. Another portion of (S)-3-chloro-propane-1 ,2-diol (55 mg,0.50 mmol) is added and stirring is continued at 70C for 24 h. The solvent is removed in vacuo and the residue is separated on prep. TLC plates with heptane:EA 2:1 to give 3-[4-((S)-2,3-dihydroxy-propoxy)-3,5-dimethyl-phenyl]-1 -(4- phenyl-5-propyl-thiophen-2-yl)-propan-1 -one (15 mg) as a colourless resin; LC-MS: tR = 1.05 min, [M+I ]+ = 453.18.

Reference： [1]Patent: WO2006/137019,2006,A1 .Location in patent: Page/Page column 39

33
3-(4-hydroxy-3,5-dimethylphenyl)-1-(4-isobutyl-3-propylthiophen-2-yl)propan-1-one [ No CAS ]
[ 60827-45-4 ]
3-[4-((S)-2,3-dihydroxypropoxy)-3,5-dimethylphenyl]-1-(4-isobutyl-3-propylthiophen-2-yl)propan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; isopropyl alcohol; at 60 - 70℃; for 24h;	To a solution of 3-(4-hydroxy-3,5-dimethyl-phenyl)-1 -(4-isobutyl-3-propyl-thiophen- 2-yl)-propan-1 -one (108 mg, 0.301 mmol) in isopropanol (5 ml_), 3 N aq. NaOH (3 ml_) followed by (S)-3-chloro-1 ,2-propanediol (167 mg, 1.51 mmol) is added. The mixture is stirred at 700C for 4 h. After 4, 5, 6, 7 and 8 h an additional portion of (S)- 3-chloro-1 ,2-propanediol (5x97 mg, 0.878 mmol) is added. After the last addition, stirring is continued at 600C for 16 h. The mixture is diluted with water and extracted with diethyl ether. The organic extract is dried over MgSO4, filtered and evaporated. The crude product is purified by prep. HPLC to give 3-[4-((S)-2,3-dihydroxy- propoxy)-3,5-dimethyl-phenyl]-1 -(4-isobutyl-3-propyl-thiophen-2-yl)-propan-1 -one (18 mg) as an almost colourless resin; LC-MS: tR = 1.09 min, [M+1] = 433.40; 1H NMR (CDCI3): delta 7.08 (s, 1 H), 6.87 (s, 2H), 4.11-4.03 (m, 1 H), 3.90-3.70 (m, 4H), 3.14-3.06 (m, 2H), 2.94-2.82 (m, 4H), 2.60 (s br, 2H), 2.40 (d, J = 7.0 Hz, 2H), 2.24 8s, 6H), 1.90-1.78 (m, 1 H), 1.56-1.46 (m, 2H), 1.00 8t, J = 7.0 Hz, 3H), 0.93 (d, J = 6.4 Hz, 6H).

Reference： [1]Patent: WO2007/80542,2007,A1 .Location in patent: Page/Page column 56

34
[ 611-20-1 ]
[ 60827-45-4 ]
[ 56715-37-8 ]

Reference： [1]Tetrahedron Asymmetry,2008,vol. 19,p. 1429 - 1434

35
[ 60827-45-4 ]
[ 146864-19-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	With thionyl chloride; In tetrachloromethane; for 2h;Reflux; Inert atmosphere;	General procedure: Thionyl chloride (0.98 mL, 1.6 mmol) was added to a suspensionof enantiomer of 3 (1.22 g, 11.0 mmol) in tetrachloromethane(15 mL) and the solution was refluxed for 2 h. The solvent was thenevaporated in vacuum and the remaining oil was purified by column chromatography using diethyl ether. 4.4 (S)-4-Chloromethyl-1,3,2-dioxathiolane 2-oxide (S)-4 From (S)-3. Yield: 1.84 g (100%, 11.0 mmol) as a colourless oil. TLC: Rf = 0.87 (diethyl ether). C3H5ClO3S (155.96) calcd: C, 23.01; H, 3.22; S, 20.48; found: C, 22.87; H, 3.30; S, 20.57. [alpha]D20 = +58.8 (c 1.515, MeOH), [alpha]D20 = +43.5 (c 1.006, CH2Cl2). Mixture of diastereoisomers 45:55. 1H NMR (300 MHz, CDCl3) delta = 3.19 (dd, J = 10.52, 8.72 Hz, 1H, CH2Cl), 3.34 (m, 1H, CH2Cl), 4.35 (dd, J = 8.85, 4.74 Hz, 1H, OCH2CH), 4.77-4.89 (m, 1H, OCH2CH), 5.05-5.17 (m, 1H, CH) (diastereoisomers 1), 3.37-3.44 (m, 1H, CH2Cl), 3.57 (dd, J = 9.75, 4.62 Hz, 1H, CH2Cl), 4.56 (dd, J = 8.72, 7.95 Hz, 1H, OCH2CH), 4.73 (dd, J = 8.98, 6,41 Hz, 1H, OCH2CH), 4.77-4.89 (m, 1H, CH) (diastereoisomers 2) ppm. 13C NMR (75.5 MHz, CDCl3) delta = 2.25 (CH2Cl), 2.53 (CH2Cl), 71.29 (CHCH2O), 71.86 (CHCH2O), 79.37 (CH), 81.69 (CH) ppm.

Reference： [1]Tetrahedron Asymmetry,2015,vol. 26,p. 1408 - 1415
[2]Letters in Organic Chemistry,2012,vol. 9,p. 520 - 521
[3]Tetrahedron Asymmetry,2009,vol. 20,p. 322 - 326

36
[ 1012305-56-4 ]
[ 60827-45-4 ]
[ 1012305-71-3 ]

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 5630 - 5640

37
[ 1012305-58-6 ]
[ 60827-45-4 ]
[ 1012305-73-5 ]

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 5630 - 5640

38
[ 60827-45-4 ]
[ 120-80-9 ]
[ 119702-04-4 ]

Reference： [1]Mendeleev Communications,2009,vol. 19,p. 208 - 210

39
[ 1186606-00-7 ]
[ 60827-45-4 ]
[ 1186606-01-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; isopropyl alcohol; at 65℃; for 40h;	To a solution of 2-ethyl-4-[5-(4-isobutyl-6-methyl-pyridin-2-yl)-[1 ,2,4]oxadiazol-3-yl]-6- methyl-phenol (41 mg, 0.1 16 mmol) in isopropanol (3 mL) and 3 N aq. NaOH (0.4 mL), (S)- 3-chloro-1 ,2-propanediol (66 mg, 0.577 mmol) is added. The mixture is stirred at 65C for16 h before another portion of (S)-3-chloro-1 ,2-propanediol (66 mg, 0.577 mmol) and 3 N <n="46"/>aq. NaOH (0.4 ml.) is added. Stirring is continued at 65C for 24 h. The mixture is cooled to rt, diluted with water, and repeatedly extracted with diethyl ether. The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified on prep. TLC using DCM:methanol 9:1 to give the title compound (16 mg) as a colourless oil; LC-MS: tR = 1.02 min, [M+H]+ = 426.17.

Reference： [1]Patent: WO2009/109872,2009,A1 .Location in patent: Page/Page column 44-45

40
[ 60827-45-4 ]
[ 124-40-3 ]
[ 666234-81-7 ]

Yield	Reaction Conditions	Operation in experiment
70%		A solution of the chlorodiol 12 (19 g, 172 mmol) and dimethylamine (250 mL of a 5.6 M ethanolic solution) was heated in a steel bomb at 120C over 18 h. TLC and MS showed no starting material. The solvent was removed and aqueous NaOH (6.9 g, 172 mmol, in 100 mL H2O) was added. The aqueous layer was washed with DCM (100 mL) then reduced to white residue. The residue was treated with 100 mL of hot EtOAc, and allowed to cool. The mixture was dried by addition of Na2SO4, then filtered. The filtrate was subjected to column chromatography to give pure 22 (14.4 g, 70 %) as a light yellow oil.

Reference： [1]Patent: WO2009/132131,2009,A1 .Location in patent: Page/Page column 103

41
heptatriaconta-6,9,28,31-tetraen-19-one [ No CAS ]
[ 60827-45-4 ]
4-(S)-4-chloromethyl-2,2-di-octadeca-9,12-dienyl-[1,3]dioxolane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With toluene-4-sulfonic acid; In benzene; for 96h;Reflux; Water removal;	A solution of compound 7 (2.7 g, 5.12 mmol), PTSA (5 mg, 0.029 mmol) and compound 12 (1 g, 9 mmol) in benzene (250 mL) was heated under reflux with Dean-Stark distillation for 48 h. TLC at this point showed that lots of starting material 7 remained. Further portions of PTSA (10 mg, 0.058 mmol) and compound 12 (1 g, 9 mmol) were added; the Dean-Stark apparatus was swapped for a Soxhlet extractor containing activated 4A molecular sieves and reflux was continued for 48 h. TLC showed mostly product at this point. Work-up by column <n="102"/>A2038-7109WO/ALN-50-WO 6 chromatography gave an inseparable mixture of 13 and 7 (ca. 9:1) (2.7 g, 85 %) as a colorless oil, which was used without further purification in the next step of the reaction.

Reference： [1]Patent: WO2009/132131,2009,A1 .Location in patent: Page/Page column 99-100

42
C₃₅H₆₆O [ No CAS ]
[ 60827-45-4 ]
4-(S)-4-chloromethyl-2,2-di-heptadec-9-enyl-[1,3]dioxolane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; for 48h;Reflux; Water removal;	A solution of compound 15 (2.0 g, 4 mmol), PTSA (10 mg, 0.029 mmol) and compound 8 (1 g, 9 mmol) in toluene (250 mL) is heated under reflux with a Soxhlet extractor containing <n="104"/>A2038-7109WO/ALN-50-WO 6 activated 4A molecular sieves for 48 h. Work-up followed by column chromatography gives the ketal 18 as a colorless oil.

Reference： [1]Patent: WO2009/132131,2009,A1 .Location in patent: Page/Page column 101-102

43
heptatriaconta-6,9,28-trien-19-one [ No CAS ]
[ 60827-45-4 ]
4-(S)-4-chloromethyl-2-octadeca-9,12-dienyl-2-octadec-9-enyl-[1,3]dioxolane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; for 48h;Reflux; Water removal;	A solution of compound 25 (2.0 g, 4 mmol), PTSA (10 mg, 0.029 mmol) and compound 12 (1 g, 9 mmol) in toluene (250 mL) is heated under reflux with a Soxhlet extractor containing activated 4A molecular sieves for 48 h. Work-up followed by column chromatography gives the ketal 30 as a colorless oil.

Reference： [1]Patent: WO2009/132131,2009,A1 .Location in patent: Page/Page column 107

44
heptatriaconta-6,9-dien-19-one [ No CAS ]
[ 60827-45-4 ]
4-(S)-4-chloromethyl-2-octadeca-9,12-dienyl-2-octadecyl-[1,3]dioxolane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; for 48h;Reflux; Water removal;	A solution of compound 27 (2.0 g, 4 mmol), PTSA (10 mg, 0.029 mmol) and compound 12 (1 g, 9 mmol) in toluene (250 mL) is heated under reflux with a Soxhlet extractor containing activated 4A molecular sieves for 48 h. Work-up followed by column chromatography gives the ketal 34 as a colorless oil.

Reference： [1]Patent: WO2009/132131,2009,A1 .Location in patent: Page/Page column 109

45
[ 1122-58-3 ]
[ 60827-45-4 ]
[ 942209-56-5 ]

Reference： [1]Synthesis,2009,p. 1437 - 1444

46
[ 60827-45-4 ]
[ 150-76-5 ]
[ 17131-52-1 ]

Reference： [1]Russian Chemical Bulletin,2008,vol. 57,p. 2320 - 2323

47
[ 60827-45-4 ]
[ 183388-44-5 ]
[ 1199789-66-6 ]

Reference： [1]Organic Letters,2010,vol. 12,p. 208 - 211

48
[ 60827-45-4 ]
[ 156942-68-6 ]
[ 1199789-49-5 ]

Reference： [1]Organic Letters,2010,vol. 12,p. 208 - 211

49
[ 371-41-5 ]
[ 60827-45-4 ]
[ 104605-96-1 ]

Yield	Reaction Conditions	Operation in experiment
84%		Example 24. Synthesis of Compounds 344 and 317.TBSCl, DMAP imidazole, CH2Cl2 Synthesis of Compound 493. A mixture of 4-fluorophenol (491; 2.36 g, 21.1 mmol) and sodium hydroxide (1.05 g, 26.3 mmol) in ethanol was heated at reflux for 15 minutes and then (^-S-chloro-l^-propanediol (492; 2.80 g, 25.3 mmol) was added and the mixture stirred at reflux for 16 h. After this time, the reaction was cooled to room temperature and concentrated. The residue was dissolved in diethyl ether (200 mL) and washed with water (75 mL) and brine (75 mL), dried over sodium sulfate, filtered and concentrated. The residue was crystallized from hexanes/diethyl ether and afforded 493 (3.30 g, 84%) as a white solid.

Reference： [1]Patent: WO2010/39531,2010,A1 .Location in patent: Page/Page column 143-144

50
[ 106-44-5 ]
[ 60827-45-4 ]
(S)-3-(4-methylphenoxy)-propane-1,2-diol [ No CAS ]

Reference： [1]Chemical Communications,2010,vol. 46,p. 3523 - 3525

51
[ 1150644-99-7 ]
[ 60827-45-4 ]
[ 1150646-28-8 ]

Yield	Reaction Conditions	Operation in experiment
	With water; sodium hydroxide; In isopropyl alcohol; at 20℃;	Examples 91, 92, 93 and 94 are prepared from Intermediate 1, 2, 3 and 4, respectively, as described below:To a solution of 1 eq. of Intermediate 1, 2, 3, or 4 (concentration: 0.02 mol/L) in iPrOH, 3M aq. NaOH followed by S-3-chloro-1,2-propanediol (10 eq.) is added. The reaction mixture is stirred at rt for 15-48 h (monitored by LC-MS), and is then diluted with EtOAc and washed with 1M aq. NaOH followed by brine. The org. solution is dried over Na2SO4, filtered, and evaporated. The crude compound is purified by prep. HPLC or prep. TLC.

Reference： [1]Patent: US2010/234346,2010,A1 .Location in patent: Page/Page column 30

52
[ 1150646-97-1 ]
[ 60827-45-4 ]
[ 1150646-88-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; isopropyl alcohol; at 20℃; for 15h;	j) To a solution of 2-ethyl-4-[5-(2-isopropylamino-6-methyl-pyrimidin-4-yl)-oxazol-2-yl]-6-methyl-phenol (30 mg, 85 mumol) in iPrOH (4 mL), 3M aq. NaOH (1 mL) followed by (S)-3-chloro-propane-1,2-diol (67 muL, 0.85 mmol) is added. The reaction mixture is stirred at rt for 15 h, and is then diluted with EtOAc and washed with 1M aq. NaOH followed by brine. The org. solution is dried over Na2SO4, filtered and evaporated to give 3-{2-ethyl-4-[5-(2-isopropylamino-6-methyl-pyrimidin-4-yl)-oxazol-2-yl]-6-methyl-phenoxy}-propane-1,2-diol (9 mg) as a yellow solid; LC-MS: tR=0.79 min, [M+H]+=426.80.

Reference： [1]Patent: US2010/234346,2010,A1 .Location in patent: Page/Page column 39

53
[ 1262414-29-8 ]
[ 60827-45-4 ]
[ 1262414-27-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; isopropyl alcohol; at 70℃; for 48h;	c) A mixture of 4-[3-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1 ,2,4]oxadiazol-5-yl]-2-ethyl-6- methyl-phenol (150 mg, 395 mumol) and (S)-3-chloro-propane-1 ,2-diol (366 mg, 3.31 mmol) in isopropanol (4 mL) and 3 N aq. NaOH (1 mL) is stirred at 700C for 48 h. The mixture is diluted with EA (50 mL), washed with 1 M aq. NaOH solution (20 mL) followed by brine (20 mL), dried over MgSO4, filtered and concentrated. The crude product is purified by prep. HPLC to give the title compound (95 mg) as a pale brown oil; LC-MS**: tR = 0.88 min, [M+H]+ = 454.08; 1H NMR (CDCI3): £ 1.34 (t, J = 7.0 Hz, 3 H), 1.67-1.79 (m, 2 H), 1.82-1.96 (m, 4 H), 2.04-2.15 (m, 2 H), 2.43 (s, 3 H), 2.79 (q, J = 7.0 Hz, 2 H), 3.18-3.29 (m, 1 H), 3.81-3.99 (m, 4 H), 4.01 (s, 3 H), 4.15-4.22 (m, 1 H), 7.30 (s, 1 H), 7.49 (s, 1 H), 7.93 (s, 1 H), 7.94 (s, 1 H).
	With water; sodium hydroxide; In isopropyl alcohol; at 70℃; for 48h;	c) A mixture of 4-[3-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-2-ethyl-6-methyl-phenol (150 mg, 395 mumol) and (S)-3-chloro-propane-1,2-diol (366 mg, 3.31 mmol) in isopropanol (4 mL) and 3 N aq. NaOH (1 mL) is stirred at 70 C. for 48 h. The mixture is diluted with EA (50 mL), washed with 1 M aq. NaOH solution (20 mL) followed by brine (20 mL), dried over MgSO4, filtered and concentrated. The crude product is purified by prep. HPLC to give the title compound (95 mg) as a pale brown oil; LC-MS**: tR=0.88 min, [M+H]+=454.08; 1H NMR (CDCl3): delta1.34 (t, J=7.0 Hz, 3H), 1.67-1.79 (m, 2H), 1.82-1.96 (m, 4H), 2.04-2.15 (m, 2H), 2.43 (s, 3H), 2.79 (q, J=7.0 Hz, 2H), 3.18-3.29 (m, 1H), 3.81-3.99 (m, 4H), 4.01 (s, 3H), 4.15-4.22 (m, 1H), 7.30 (s, 1H), 7.49 (s, 1H), 7.93 (s, 1 H), 7.94 (s, 1H).

Reference： [1]Patent: WO2011/7324,2011,A1 .Location in patent: Page/Page column 36
[2]Patent: US2012/108638,2012,A1 .Location in patent: Page/Page column 15

54
[ 1262414-37-8 ]
[ 60827-45-4 ]
[ 1262414-35-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; isopropyl alcohol; at 70℃; for 48h;	c) A mixture of 4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1 ,3,4]oxadiazol-2-yl]-2-ethyl-6- methyl-phenol (100 mg, 264 mumol) and (S)-3-chloro-propane-1 ,2-diol (244 mg, 2.64 mmol) in isopropanol (4 ml.) and 3 N aq. NaOH (1 ml.) is stirred at 700C for 48 h. The mixture is diluted with EA (50 ml_), washed with 1 M aq. NaOH solution (20 ml.) followed by brine (20 ml_), dried over MgSO4, filtered and concentrated. The crude product is purified by prep. HPLC to give the title compound (86 mg) as a white solid; LC-MS**: tR = 0.83 min, [M+H]+ = 454.12; 1H NMR (CDCI3): £1.33 (t, J = 7.5 Hz, 3 H), 1.65-1.80 (m, 2 H), 1.83-1.96 (m, 4 H), 2.05-2.15 (m, 2 H), 2.42 (s, 3 H), 2.78 (q, J = 7.3 Hz, 2 H), 3.19-3.30 (m, 1 H), 3.82-3.99 (m, 4 H), 4.02 (s, 3 H), 4.15-4.23 (m, 1 H), 7.22 (s, 1 H), 7.48 (s, 1 H), 7.84 (s, 1 H), 7.86 (s, 1 H).
	With water; sodium hydroxide; In isopropyl alcohol; at 70℃; for 48h;	c) A mixture of 4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,3,4]oxadiazol-2-yl]-2-ethyl-6-methyl-phenol (100 mg, 264 mumol) and (S)-3-chloro-propane-1,2-diol (244 mg, 2.64 mmol) in isopropanol (4 mL) and 3 N aq. NaOH (1 mL) is stirred at 70 C. for 48 h. The mixture is diluted with EA (50 mL), washed with 1 M aq. NaOH solution (20 mL) followed by brine (20 mL), dried over MgSO4, filtered and concentrated. The crude product is purified by prep. HPLC to give the title compound (86 mg) as a white solid; LC-MS**: tR=0.83 min, [M+H]+=454.12; 1H NMR (CDCl3): delta1.33 (t, J=7.5 Hz, 3H), 1.65-1.80 (m, 2H), 1.83-1.96 (m, 4H), 2.05-2.15 (m, 2H), 2.42 (s, 3H), 2.78 (q, J=7.3 Hz, 2H), 3.19-3.30 (m, 1H), 3.82-3.99 (m, 4H), 4.02 (s, 3H), 4.15-4.23 (m, 1H), 7.22 (s, 1H), 7.48 (s, 1H), 7.84 (s, 1H), 7.86 (s, 1H).

Reference： [1]Patent: WO2011/7324,2011,A1 .Location in patent: Page/Page column 39
[2]Patent: US2012/108638,2012,A1 .Location in patent: Page/Page column 16

55
[ 1263400-68-5 ]
[ 60827-45-4 ]
[ 1263400-61-8 ]

Yield	Reaction Conditions	Operation in experiment
		8-(tert-butylamino)-6-chloro-2,7-naphthyridin-l(2H)-one (3g , 12 mmol) was added in a suspension of Cs2CO3 (11.5g, 36 mmol) in DMF (25 mL). The solution was stirred for 30 minutes and (S)- 3-chloropropane-1,2-diol (2.64 g, 24 mmol) was added into the solution. The stirring was continued for 30 hours and poured into ice cold water. The reaction mixture was worked up with ethyl acetate and purified by silica gel column chromatography by using DCMMeOH (10:1) as eluent to obtain (R)-8-(tert- butylamino)-6-chloro-2-(2,3-dihydroxypropyl)-2,7-naphthyridin-l(2H)-one. 1H NMR (MeOH-Cf4) delta 9.70 (s, 1H), 7.40 (d, J=7.2, 1H), 6.84 (s, 1H), 6.30 (d, J=7.2 Hz, 1H), 4.28 (m, 1H), 3.96 (m, 1H), 3.73 (m, 1H), 3.55 (m, 2H), 3.31 (m, 1H), 1.50 (s, 9H), ESI-MS (m/z) 326.12(MH+).

Reference： [1]Patent: WO2011/14515,2011,A1 .Location in patent: Page/Page column 120-121

56
[ 60827-45-4 ]
[ 70-11-1 ]
[ 1207291-11-9 ]
[ 1207291-10-8 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; at 130℃;Product distribution / selectivity;	Example 23; Synthesis of (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange between substrates A mixture of 2-bromo-4'-chloroacetophenone (4.94 g, 2-chloro-4'-chloroacetophenone content=0.09%), p-toluenesulfonic acid monohydrate (0.20 g, 0.05 equivalent) and toluene (100 mL) was refluxed at 130C using an azeotropic distillation device with a Dean-Stark tube, and (S)-monochlorohydrin (2.59 g, 1.1 equivalents, >99%ee) was added dropwise under reflux such that the amount of the (S)-monochlorohydrin present in the reaction solution would be not more than 0.1 equivalent (not more than 2.1 mmol) relative to the amount of 2-bromo-4'-chloroacetophenone to be used (21.2 mmol), while analyzing the progress of the reaction by GC. After confirmation of the completion of the azeotropic distillation, the reaction mixture was cooled and washed with 10% aqueous sodium hydrogen carbonate solution and 10% brine. The solvent was evaporated under reduced pressure to give (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane (6.56 g, >99%ee). Here, the content percentage of (4S)-trans-,cis-2-(4-chlorophenyl)-2-chloromethyl-4-chloromethyl-1,3-dioxolane halogen-exchanged with a chlorine atom was 0.09%. Examples 30 to 41 Synthesis of (4S)-trans-cis-2-aryl-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange In Examples 30 to 41, reactions were performed according to Example 23 and using aryl(bromomethyl)ketones (halogen-exchanged compound content<0.1%) shown in Table 7 and Table 8. The results are shown in Table 9 and Table 10 together with Example 23.

Reference： [1]Patent: EP2325178,2011,A1 .Location in patent: Page/Page column 28; 31

57
[ 60827-45-4 ]
[ 403-29-2 ]
[ 1207291-02-8 ]
[ 1207291-01-7 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; at 130℃;Product distribution / selectivity;	Example 23; Synthesis of (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange between substrates A mixture of 2-bromo-4'-chloroacetophenone (4.94 g, 2-chloro-4'-chloroacetophenone content=0.09%), p-toluenesulfonic acid monohydrate (0.20 g, 0.05 equivalent) and toluene (100 mL) was refluxed at 130C using an azeotropic distillation device with a Dean-Stark tube, and (S)-monochlorohydrin (2.59 g, 1.1 equivalents, >99%ee) was added dropwise under reflux such that the amount of the (S)-monochlorohydrin present in the reaction solution would be not more than 0.1 equivalent (not more than 2.1 mmol) relative to the amount of 2-bromo-4'-chloroacetophenone to be used (21.2 mmol), while analyzing the progress of the reaction by GC. After confirmation of the completion of the azeotropic distillation, the reaction mixture was cooled and washed with 10% aqueous sodium hydrogen carbonate solution and 10% brine. The solvent was evaporated under reduced pressure to give (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane (6.56 g, >99%ee). Here, the content percentage of (4S)-trans-,cis-2-(4-chlorophenyl)-2-chloromethyl-4-chloromethyl-1,3-dioxolane halogen-exchanged with a chlorine atom was 0.09%. Examples 30 to 41 Synthesis of (4S)-trans-cis-2-aryl-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange In Examples 30 to 41, reactions were performed according to Example 23 and using aryl(bromomethyl)ketones (halogen-exchanged compound content<0.1%) shown in Table 7 and Table 8. The results are shown in Table 9 and Table 10 together with Example 23.

Reference： [1]Patent: EP2325178,2011,A1 .Location in patent: Page/Page column 28; 30

58
[ 60827-45-4 ]
[ 619-41-0 ]
[ 1207291-14-2 ]
[ 1207291-13-1 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; at 130℃;Product distribution / selectivity;	Example 23; Synthesis of (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange between substrates A mixture of 2-bromo-4'-chloroacetophenone (4.94 g, 2-chloro-4'-chloroacetophenone content=0.09%), p-toluenesulfonic acid monohydrate (0.20 g, 0.05 equivalent) and toluene (100 mL) was refluxed at 130C using an azeotropic distillation device with a Dean-Stark tube, and (S)-monochlorohydrin (2.59 g, 1.1 equivalents, >99%ee) was added dropwise under reflux such that the amount of the (S)-monochlorohydrin present in the reaction solution would be not more than 0.1 equivalent (not more than 2.1 mmol) relative to the amount of 2-bromo-4'-chloroacetophenone to be used (21.2 mmol), while analyzing the progress of the reaction by GC. After confirmation of the completion of the azeotropic distillation, the reaction mixture was cooled and washed with 10% aqueous sodium hydrogen carbonate solution and 10% brine. The solvent was evaporated under reduced pressure to give (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane (6.56 g, >99%ee). Here, the content percentage of (4S)-trans-,cis-2-(4-chlorophenyl)-2-chloromethyl-4-chloromethyl-1,3-dioxolane halogen-exchanged with a chlorine atom was 0.09%. Examples 30 to 41 Synthesis of (4S)-trans-cis-2-aryl-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange In Examples 30 to 41, reactions were performed according to Example 23 and using aryl(bromomethyl)ketones (halogen-exchanged compound content<0.1%) shown in Table 7 and Table 8. The results are shown in Table 9 and Table 10 together with Example 23.

Reference： [1]Patent: EP2325178,2011,A1 .Location in patent: Page/Page column 28; 31

59
[ 60827-45-4 ]
[ 536-38-9 ]
[ 1207290-96-7 ]
[ 1207290-97-8 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; at 130℃;Product distribution / selectivity;	Example 23; Synthesis of (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange between substrates A mixture of 2-bromo-4'-chloroacetophenone (4.94 g, 2-chloro-4'-chloroacetophenone content=0.09%), p-toluenesulfonic acid monohydrate (0.20 g, 0.05 equivalent) and toluene (100 mL) was refluxed at 130C using an azeotropic distillation device with a Dean-Stark tube, and (S)-monochlorohydrin (2.59 g, 1.1 equivalents, >99%ee) was added dropwise under reflux such that the amount of the (S)-monochlorohydrin present in the reaction solution would be not more than 0.1 equivalent (not more than 2.1 mmol) relative to the amount of 2-bromo-4'-chloroacetophenone to be used (21.2 mmol), while analyzing the progress of the reaction by GC. After confirmation of the completion of the azeotropic distillation, the reaction mixture was cooled and washed with 10% aqueous sodium hydrogen carbonate solution and 10% brine. The solvent was evaporated under reduced pressure to give (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane (6.56 g, >99%ee). Here, the content percentage of (4S)-trans-,cis-2-(4-chlorophenyl)-2-chloromethyl-4-chloromethyl-1,3-dioxolane halogen-exchanged with a chlorine atom was 0.09%.

Reference： [1]Patent: EP2325178,2011,A1 .Location in patent: Page/Page column 28; 30

60
[ 60827-45-4 ]
[ 613-54-7 ]
[ 1207291-20-0 ]
[ 1207291-19-7 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; at 130℃;Product distribution / selectivity;	Example 23; Synthesis of (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange between substrates A mixture of 2-bromo-4'-chloroacetophenone (4.94 g, 2-chloro-4'-chloroacetophenone content=0.09%), p-toluenesulfonic acid monohydrate (0.20 g, 0.05 equivalent) and toluene (100 mL) was refluxed at 130C using an azeotropic distillation device with a Dean-Stark tube, and (S)-monochlorohydrin (2.59 g, 1.1 equivalents, >99%ee) was added dropwise under reflux such that the amount of the (S)-monochlorohydrin present in the reaction solution would be not more than 0.1 equivalent (not more than 2.1 mmol) relative to the amount of 2-bromo-4'-chloroacetophenone to be used (21.2 mmol), while analyzing the progress of the reaction by GC. After confirmation of the completion of the azeotropic distillation, the reaction mixture was cooled and washed with 10% aqueous sodium hydrogen carbonate solution and 10% brine. The solvent was evaporated under reduced pressure to give (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane (6.56 g, >99%ee). Here, the content percentage of (4S)-trans-,cis-2-(4-chlorophenyl)-2-chloromethyl-4-chloromethyl-1,3-dioxolane halogen-exchanged with a chlorine atom was 0.09%. Examples 30 to 41 Synthesis of (4S)-trans-cis-2-aryl-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange In Examples 30 to 41, reactions were performed according to Example 23 and using aryl(bromomethyl)ketones (halogen-exchanged compound content<0.1%) shown in Table 7 and Table 8. The results are shown in Table 9 and Table 10 together with Example 23.

Reference： [1]Patent: EP2325178,2011,A1 .Location in patent: Page/Page column 28; 31

61
[ 60827-45-4 ]
[ 2632-13-5 ]
[ 1207291-23-3 ]
[ 1207291-22-2 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; at 130℃;Product distribution / selectivity;	Example 23; Synthesis of (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange between substrates A mixture of 2-bromo-4'-chloroacetophenone (4.94 g, 2-chloro-4'-chloroacetophenone content=0.09%), p-toluenesulfonic acid monohydrate (0.20 g, 0.05 equivalent) and toluene (100 mL) was refluxed at 130C using an azeotropic distillation device with a Dean-Stark tube, and (S)-monochlorohydrin (2.59 g, 1.1 equivalents, >99%ee) was added dropwise under reflux such that the amount of the (S)-monochlorohydrin present in the reaction solution would be not more than 0.1 equivalent (not more than 2.1 mmol) relative to the amount of 2-bromo-4'-chloroacetophenone to be used (21.2 mmol), while analyzing the progress of the reaction by GC. After confirmation of the completion of the azeotropic distillation, the reaction mixture was cooled and washed with 10% aqueous sodium hydrogen carbonate solution and 10% brine. The solvent was evaporated under reduced pressure to give (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane (6.56 g, >99%ee). Here, the content percentage of (4S)-trans-,cis-2-(4-chlorophenyl)-2-chloromethyl-4-chloromethyl-1,3-dioxolane halogen-exchanged with a chlorine atom was 0.09%. Examples 30 to 41 Synthesis of (4S)-trans-cis-2-aryl-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange In Examples 30 to 41, reactions were performed according to Example 23 and using aryl(bromomethyl)ketones (halogen-exchanged compound content<0.1%) shown in Table 7 and Table 8. The results are shown in Table 9 and Table 10 together with Example 23.

Reference： [1]Patent: EP2325178,2011,A1 .Location in patent: Page/Page column 28; 32

62
[ 60827-45-4 ]
[ 99-81-0 ]
[ 1207291-29-9 ]
[ 1207291-28-8 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; at 130℃;Product distribution / selectivity;	Example 23; Synthesis of (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange between substrates A mixture of 2-bromo-4'-chloroacetophenone (4.94 g, 2-chloro-4'-chloroacetophenone content=0.09%), p-toluenesulfonic acid monohydrate (0.20 g, 0.05 equivalent) and toluene (100 mL) was refluxed at 130C using an azeotropic distillation device with a Dean-Stark tube, and (S)-monochlorohydrin (2.59 g, 1.1 equivalents, >99%ee) was added dropwise under reflux such that the amount of the (S)-monochlorohydrin present in the reaction solution would be not more than 0.1 equivalent (not more than 2.1 mmol) relative to the amount of 2-bromo-4'-chloroacetophenone to be used (21.2 mmol), while analyzing the progress of the reaction by GC. After confirmation of the completion of the azeotropic distillation, the reaction mixture was cooled and washed with 10% aqueous sodium hydrogen carbonate solution and 10% brine. The solvent was evaporated under reduced pressure to give (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane (6.56 g, >99%ee). Here, the content percentage of (4S)-trans-,cis-2-(4-chlorophenyl)-2-chloromethyl-4-chloromethyl-1,3-dioxolane halogen-exchanged with a chlorine atom was 0.09%. Examples 30 to 41 Synthesis of (4S)-trans-cis-2-aryl-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange In Examples 30 to 41, reactions were performed according to Example 23 and using aryl(bromomethyl)ketones (halogen-exchanged compound content<0.1%) shown in Table 7 and Table 8. The results are shown in Table 9 and Table 10 together with Example 23.

Reference： [1]Patent: EP2325178,2011,A1 .Location in patent: Page/Page column 28; 32

63
[ 60827-45-4 ]
[ 102429-07-2 ]
[ 1207291-05-1 ]
[ 1207291-04-0 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; at 130℃;Product distribution / selectivity;	Example 23; Synthesis of (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange between substrates A mixture of 2-bromo-4'-chloroacetophenone (4.94 g, 2-chloro-4'-chloroacetophenone content=0.09%), p-toluenesulfonic acid monohydrate (0.20 g, 0.05 equivalent) and toluene (100 mL) was refluxed at 130C using an azeotropic distillation device with a Dean-Stark tube, and (S)-monochlorohydrin (2.59 g, 1.1 equivalents, >99%ee) was added dropwise under reflux such that the amount of the (S)-monochlorohydrin present in the reaction solution would be not more than 0.1 equivalent (not more than 2.1 mmol) relative to the amount of 2-bromo-4'-chloroacetophenone to be used (21.2 mmol), while analyzing the progress of the reaction by GC. After confirmation of the completion of the azeotropic distillation, the reaction mixture was cooled and washed with 10% aqueous sodium hydrogen carbonate solution and 10% brine. The solvent was evaporated under reduced pressure to give (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane (6.56 g, >99%ee). Here, the content percentage of (4S)-trans-,cis-2-(4-chlorophenyl)-2-chloromethyl-4-chloromethyl-1,3-dioxolane halogen-exchanged with a chlorine atom was 0.09%. Examples 30 to 41 Synthesis of (4S)-trans-cis-2-aryl-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange In Examples 30 to 41, reactions were performed according to Example 23 and using aryl(bromomethyl)ketones (halogen-exchanged compound content<0.1%) shown in Table 7 and Table 8. The results are shown in Table 9 and Table 10 together with Example 23.

Reference： [1]Patent: EP2325178,2011,A1 .Location in patent: Page/Page column 28; 31

64
[ 60827-45-4 ]
[ 28179-33-1 ]
[ 1207291-26-6 ]
[ 1207291-25-5 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; at 130℃;Product distribution / selectivity;	Example 23; Synthesis of (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange between substrates A mixture of 2-bromo-4'-chloroacetophenone (4.94 g, 2-chloro-4'-chloroacetophenone content=0.09%), p-toluenesulfonic acid monohydrate (0.20 g, 0.05 equivalent) and toluene (100 mL) was refluxed at 130C using an azeotropic distillation device with a Dean-Stark tube, and (S)-monochlorohydrin (2.59 g, 1.1 equivalents, >99%ee) was added dropwise under reflux such that the amount of the (S)-monochlorohydrin present in the reaction solution would be not more than 0.1 equivalent (not more than 2.1 mmol) relative to the amount of 2-bromo-4'-chloroacetophenone to be used (21.2 mmol), while analyzing the progress of the reaction by GC. After confirmation of the completion of the azeotropic distillation, the reaction mixture was cooled and washed with 10% aqueous sodium hydrogen carbonate solution and 10% brine. The solvent was evaporated under reduced pressure to give (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane (6.56 g, >99%ee). Here, the content percentage of (4S)-trans-,cis-2-(4-chlorophenyl)-2-chloromethyl-4-chloromethyl-1,3-dioxolane halogen-exchanged with a chlorine atom was 0.09%. Examples 30 to 41 Synthesis of (4S)-trans-cis-2-aryl-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange In Examples 30 to 41, reactions were performed according to Example 23 and using aryl(bromomethyl)ketones (halogen-exchanged compound content<0.1%) shown in Table 7 and Table 8. The results are shown in Table 9 and Table 10 together with Example 23.

Reference： [1]Patent: EP2325178,2011,A1 .Location in patent: Page/Page column 28; 32

65
[ 60827-45-4 ]
[ 135-73-9 ]
[ 1207291-17-5 ]
[ 1207291-16-4 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; at 130℃;Product distribution / selectivity;	Example 23; Synthesis of (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange between substrates A mixture of 2-bromo-4'-chloroacetophenone (4.94 g, 2-chloro-4'-chloroacetophenone content=0.09%), p-toluenesulfonic acid monohydrate (0.20 g, 0.05 equivalent) and toluene (100 mL) was refluxed at 130C using an azeotropic distillation device with a Dean-Stark tube, and (S)-monochlorohydrin (2.59 g, 1.1 equivalents, >99%ee) was added dropwise under reflux such that the amount of the (S)-monochlorohydrin present in the reaction solution would be not more than 0.1 equivalent (not more than 2.1 mmol) relative to the amount of 2-bromo-4'-chloroacetophenone to be used (21.2 mmol), while analyzing the progress of the reaction by GC. After confirmation of the completion of the azeotropic distillation, the reaction mixture was cooled and washed with 10% aqueous sodium hydrogen carbonate solution and 10% brine. The solvent was evaporated under reduced pressure to give (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane (6.56 g, >99%ee). Here, the content percentage of (4S)-trans-,cis-2-(4-chlorophenyl)-2-chloromethyl-4-chloromethyl-1,3-dioxolane halogen-exchanged with a chlorine atom was 0.09%. Examples 30 to 41 Synthesis of (4S)-trans-cis-2-aryl-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange In Examples 30 to 41, reactions were performed according to Example 23 and using aryl(bromomethyl)ketones (halogen-exchanged compound content<0.1%) shown in Table 7 and Table 8. The results are shown in Table 9 and Table 10 together with Example 23.

Reference： [1]Patent: EP2325178,2011,A1 .Location in patent: Page/Page column 28; 31

66
[ 60827-45-4 ]
[ 2631-72-3 ]
[ 170210-45-4 ]
[ 170210-44-3 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; at 130℃;Product distribution / selectivity;	Example 23; Synthesis of (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange between substrates A mixture of 2-bromo-4'-chloroacetophenone (4.94 g, 2-chloro-4'-chloroacetophenone content=0.09%), p-toluenesulfonic acid monohydrate (0.20 g, 0.05 equivalent) and toluene (100 mL) was refluxed at 130C using an azeotropic distillation device with a Dean-Stark tube, and (S)-monochlorohydrin (2.59 g, 1.1 equivalents, >99%ee) was added dropwise under reflux such that the amount of the (S)-monochlorohydrin present in the reaction solution would be not more than 0.1 equivalent (not more than 2.1 mmol) relative to the amount of 2-bromo-4'-chloroacetophenone to be used (21.2 mmol), while analyzing the progress of the reaction by GC. After confirmation of the completion of the azeotropic distillation, the reaction mixture was cooled and washed with 10% aqueous sodium hydrogen carbonate solution and 10% brine. The solvent was evaporated under reduced pressure to give (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane (6.56 g, >99%ee). Here, the content percentage of (4S)-trans-,cis-2-(4-chlorophenyl)-2-chloromethyl-4-chloromethyl-1,3-dioxolane halogen-exchanged with a chlorine atom was 0.09%. Examples 30 to 41 Synthesis of (4S)-trans-cis-2-aryl-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange In Examples 30 to 41, reactions were performed according to Example 23 and using aryl(bromomethyl)ketones (halogen-exchanged compound content<0.1%) shown in Table 7 and Table 8. The results are shown in Table 9 and Table 10 together with Example 23.

Reference： [1]Patent: EP2325178,2011,A1 .Location in patent: Page/Page column 28; 30

67
[ 10531-41-6 ]
[ 60827-45-4 ]
[ 1207291-32-4 ]
[ 1207291-31-3 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; at 130℃;Product distribution / selectivity;	Example 23; Synthesis of (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange between substrates A mixture of 2-bromo-4'-chloroacetophenone (4.94 g, 2-chloro-4'-chloroacetophenone content=0.09%), p-toluenesulfonic acid monohydrate (0.20 g, 0.05 equivalent) and toluene (100 mL) was refluxed at 130C using an azeotropic distillation device with a Dean-Stark tube, and (S)-monochlorohydrin (2.59 g, 1.1 equivalents, >99%ee) was added dropwise under reflux such that the amount of the (S)-monochlorohydrin present in the reaction solution would be not more than 0.1 equivalent (not more than 2.1 mmol) relative to the amount of 2-bromo-4'-chloroacetophenone to be used (21.2 mmol), while analyzing the progress of the reaction by GC. After confirmation of the completion of the azeotropic distillation, the reaction mixture was cooled and washed with 10% aqueous sodium hydrogen carbonate solution and 10% brine. The solvent was evaporated under reduced pressure to give (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane (6.56 g, >99%ee). Here, the content percentage of (4S)-trans-,cis-2-(4-chlorophenyl)-2-chloromethyl-4-chloromethyl-1,3-dioxolane halogen-exchanged with a chlorine atom was 0.09%. Examples 30 to 41 Synthesis of (4S)-trans-cis-2-aryl-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange In Examples 30 to 41, reactions were performed according to Example 23 and using aryl(bromomethyl)ketones (halogen-exchanged compound content<0.1%) shown in Table 7 and Table 8. The results are shown in Table 9 and Table 10 together with Example 23.

Reference： [1]Patent: EP2325178,2011,A1 .Location in patent: Page/Page column 28; 32

68
[ 86520-33-4 ]
[ 60827-45-4 ]
[ 1207291-08-4 ]
[ 1207291-07-3 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; In toluene; at 130℃;Product distribution / selectivity;	Example 23; Synthesis of (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange between substrates A mixture of 2-bromo-4'-chloroacetophenone (4.94 g, 2-chloro-4'-chloroacetophenone content=0.09%), p-toluenesulfonic acid monohydrate (0.20 g, 0.05 equivalent) and toluene (100 mL) was refluxed at 130C using an azeotropic distillation device with a Dean-Stark tube, and (S)-monochlorohydrin (2.59 g, 1.1 equivalents, >99%ee) was added dropwise under reflux such that the amount of the (S)-monochlorohydrin present in the reaction solution would be not more than 0.1 equivalent (not more than 2.1 mmol) relative to the amount of 2-bromo-4'-chloroacetophenone to be used (21.2 mmol), while analyzing the progress of the reaction by GC. After confirmation of the completion of the azeotropic distillation, the reaction mixture was cooled and washed with 10% aqueous sodium hydrogen carbonate solution and 10% brine. The solvent was evaporated under reduced pressure to give (4S)-trans-,cis-2-(4-chlorophenyl)-2-bromomethyl-4-chloromethyl-1,3-dioxolane (6.56 g, >99%ee). Here, the content percentage of (4S)-trans-,cis-2-(4-chlorophenyl)-2-chloromethyl-4-chloromethyl-1,3-dioxolane halogen-exchanged with a chlorine atom was 0.09%. Examples 30 to 41 Synthesis of (4S)-trans-cis-2-aryl-2-bromomethyl-4-chloromethyl-1,3-dioxolane suppressing halogen exchange In Examples 30 to 41, reactions were performed according to Example 23 and using aryl(bromomethyl)ketones (halogen-exchanged compound content<0.1%) shown in Table 7 and Table 8. The results are shown in Table 9 and Table 10 together with Example 23.

Reference： [1]Patent: EP2325178,2011,A1 .Location in patent: Page/Page column 28; 31

69
[ 60827-45-4 ]
[ 121-51-7 ]
[ 115314-14-2 ]

Reference： [1]Beilstein Journal of Organic Chemistry,2012,vol. 8,p. 1700 - 1704

70
[ 1260162-49-9 ]
[ 60827-45-4 ]
[ 1260163-18-5 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 10090 - 10107

71
hydroxycobalamine [ No CAS ]
[ 60827-45-4 ]
(S)-2,3-dihydroxypropylcobalamin [ No CAS ]

Reference： [1]Chemistry - A European Journal,2012,vol. 18,p. 16114 - 16122

72
[ 60827-45-4 ]
[ 150-76-5 ]
[ 61248-76-8 ]

Reference： [1]Journal of Molecular Structure,2013,vol. 1032,p. 176 - 184

73
[ 90-15-3 ]
[ 60827-45-4 ]
[ 56715-19-6 ]

Reference： [1]Journal of Molecular Structure,2013,vol. 1045,p. 104 - 111

74
[ 2380-94-1 ]
[ 60827-45-4 ]
[ 80183-74-0 ]

Yield	Reaction Conditions	Operation in experiment
80%		General procedure: (S)-3-(4-Indolyloxy)-propane-1,2-diol, (S)-4 was preparedfrom 250 mg (1.9 mmol) 4-hydroxyindole and (S)-3-chloropropane-1,2-diol (0.243 g, 2.2 mmol), as described above for rac-4.The yield was 310 mg (80%); mp 122 C (Et2O-MeCN, 3:1 v/v);a20D = +5.2 (c 1.49, MeOH); 96% ee {lit. [9]: mp 119-120 C;a20D = +5.1 (c 1.47, MeOH)}. 1H and 13C NMR spectra were identicalwith that cited above for rac-4

Reference： [1]Journal of Molecular Structure,2013,vol. 1045,p. 104 - 111

75
[ 1313613-18-1 ]
[ 60827-45-4 ]
[ 1117893-60-3 ]

Yield	Reaction Conditions	Operation in experiment
74.8%	With lithium tert-butoxide; In tetrahydrofuran; at 30℃; for 24h;	Example 2: Preparation of 4-(4-((R)-5-(hydroxymethyl)-2-oxo-oxazolidin-3- yl)phenyl)morpholin-3-one (Compound-V): 3.0g, (9.20 mmol) of [4-(3-oxo-morphoin-4-yl) phenyl] carbamic acid benzyl ester and 25 ml of anhydrous tetrahydrofuran (THF) were charged in a clean and dry R.B. flask. Lithium-t-butoxide in tetrahydrofuran (THF) (1.0 MjJ jnl^LS^-mmoO-was-added-drop^" wise followed by addition of S-(+)-3-chloro-l,2-propane diol (1.22g, 1 1 mmol) The resultant reaction mixture was stirred at about 30C for about 24hours. The reaction mixture was diluted by adding 20ml of saturated ammonium chloride solution and tetrahydrofuran (THF) was evaporated under reduced pressure. The aqeous phase was extracted with dichloromethane (5 X 20 ml). The combined organic phases were dried over anhydrous magnesium sulphate. The solvent was distilled completely at about 30C under vacuum. The crude obtained was suspended in 10 ml of ethyl acetate followed by heating to about reflux for about 30 min. The reaction suspension was cooled to about 30C. The solid separated was filtered and the solid was washed with 2 ml of ethyl acetate to afford the title compound as light brownish solid. Yield : 2.0 gms, (% Yield: 74.8%).

Reference： [1]Patent: WO2013/105100,2013,A1 .Location in patent: Page/Page column 50

76
[ 60827-45-4 ]
[ 141-75-3 ]
[ 1447919-66-5 ]

Yield	Reaction Conditions	Operation in experiment
72.1%	With triethylamine; In dichloromethane; at 0 - 30℃;	Step I: Preparation of (S)-Butyric acid-2-butyryloxy-l-(chIoromethyl)-ethyl ester (Compound -VII, where R5 = R6 = -CO-C3H7 and W=-C1): 1 1.05g, (0.1 mol) of S-(+)-3-chloro-l ,2-propanediol and 100ml of dichloromethane were charged into a clean and dry R.B.flask. 30.3g, (0.3 mol) of triethylamine was added and cooled to about 0C. 24.5g (0.23 mol) of butyryl chloride was added drop-wise. The resultant reaction mixture was brought to about 30C and stirred for over-night. The organic layer was washed with dil.HCl (20 ml x 2), water (20 ml) and saturated sodium bicarbonate solution (20 ml x 2). The organic and aqeous layers were separated and the organic layer was dried over anhydrous sodium sulfate. The organic layer was distilled completely under vacuum to afford the title compound as colorless liquid. Yield: 16,89g, (% Yield: 72.1%).

Reference： [1]Patent: WO2013/105100,2013,A1 .Location in patent: Page/Page column 51-52

77
[ 60827-45-4 ]
[ 13064-64-7 ]
(2S,2'S)-3,3'-((2,5-diiodo-1,4-phenylene)bis(oxy))bis(propane-1,2-diol) [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2013,vol. 52,p. 7958 - 7962
Angew. Chem.,2013,vol. 125,p. 8116 - 8120

78
2,6-dimethyl-4-[3-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-[1,2,4]oxadiazol-5-yl]-phenol [ No CAS ]
[ 60827-45-4 ]
(S)-3-(2,6-dimethyl-4-(3-((3bS,4aR)-3,4,4-trimethyl-3b,4,4a,5-tetrahydrocyclopropa[3,4]cyclopenta[1,2-c]thiophen-1-yl)-1,2,4-oxadiazol-5-yl)phenoxy)propane-1,2-diol [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 9737 - 9755

79
[ 875013-01-7 ]
[ 60827-45-4 ]
3-(4-((S)-2,3-dihydroxypropoxy)-3,5-dimethylphenyl)-1-((3bS,4aR)-3,4,4-trimethyl-3b,4,4a,5-tetrahydrocyclopropa[3,4]cyclopenta[1,2-c]thiophen-1-yl)propan-1-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 9737 - 9755

80
[ 1062669-89-9 ]
[ 60827-45-4 ]
[ 1062669-94-6 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 110 - 130

81
[ 1062671-19-5 ]
[ 60827-45-4 ]
[ 1062671-27-5 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 110 - 130

82
[ 910636-06-5 ]
[ 60827-45-4 ]
(S)-3-(4-(2,3-dihydroxypropoxy)-3,5-dimethylphenyl)-1-(3,5,5-trimethyl-4,5,6,7-tetrahydrobenzo[c]thiophen-1-yl)propan-1-one [ No CAS ]