[ CAS No. 300-85-6 ] {[proInfo.proName]}

Name: 300-85-6|DL-3-Hydroxybutyric Acid|80%
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Quality Control of [ 300-85-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 300-85-6 ]

Product Details of [ 300-85-6 ]

CAS No. :	300-85-6	MDL No. :	MFCD00004546
Formula :	C₄H₈O₃	Boiling Point :	-
Linear Structure Formula :	CH₃CHOHCH₂CO₂H	InChI Key :	WHBMMWSBFZVSSR-UHFFFAOYSA-N
M.W :	104.10	Pubchem ID :	441
Synonyms :	β-Hydroxybutyric acid;(±)-β-Hydroxybutyrate;βOHB;NSC 3806;BHB;3-hydroxybutanoic acid	Chemical Name :	DL-3-Hydroxybutyric Acid

Calculated chemistry of [ 300-85-6 ] Expand+

Physicochemical Properties

Num. heavy atoms :	7
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.75
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	24.28
TPSA :	57.53 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) :	-7.31 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.63
Log Po/w (XLOGP3) :	-0.53
Log Po/w (WLOGP) :	-0.16
Log Po/w (MLOGP) :	-0.39
Log Po/w (SILICOS-IT) :	-0.49
Consensus Log Po/w :	-0.19

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-0.02
Solubility :	99.5 mg/ml ; 0.956 mol/l
Class :	Very soluble
Log S (Ali) :	-0.21
Solubility :	64.3 mg/ml ; 0.618 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	0.55
Solubility :	372.0 mg/ml ; 3.57 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.55

Safety of [ 300-85-6 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 300-85-6 ]

* 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 [ 300-85-6 ]
Downstream synthetic route of [ 300-85-6 ]

[ 300-85-6 ] Synthesis Path-Upstream 1~1

1
[ 156-43-4 ]
[ 300-85-6 ]
[ 1083-57-4 ]

Reference： [1] Organic Letters, 2018, vol. 20, # 23, p. 7371 - 7374

[ 300-85-6 ] Synthesis Path-Downstream 1~109

1
[ 110-86-1 ]
[ 60-29-7 ]
[ 141-82-2 ]
[ 75-07-0 ]
[ 3724-65-0 ]
[ 300-85-6 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1923,vol. 432,p. 65

2
[ 3068-88-0 ]
[ 300-85-6 ]

Reference： [1]Chemische Berichte,1915,vol. 48,p. 1264
Chemisches Zentralblatt,1916,vol. 87,p. 557
[2]Chemische Berichte,1915,vol. 48,p. 1264
Chemisches Zentralblatt,1916,vol. 87,p. 557
[3]Journal of Organic Chemistry,2005,vol. 70,p. 420 - 426
[4]Journal of Solution Chemistry,2008,vol. 37,p. 451 - 457

3
[ 625-38-7 ]
furan-2,3,5(4H)-trione pyridine (1:1) [ No CAS ]
[ 3724-65-0 ]
[ 300-85-6 ]

Reference： [1]Chemische Berichte,1902,vol. 35,p. 940

4
[ 625-38-7 ]
[ 107-93-7 ]
[ 300-85-6 ]

Reference： [1]Chemische Berichte,1902,vol. 35,p. 940

5
[ 64584-92-5 ]
[ 300-85-6 ]

Reference： [1]Journal of Biological Chemistry,1929,vol. 81,p. 427
Science (Washington, DC, United States),vol. 69,p. 47
Chemisches Zentralblatt,1929,vol. 100,p. 1211

6
[ 4368-06-3 ]
[ 300-85-6 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1870,vol. 153,p. 241

7
[ 1190-76-7 ]
[ 300-85-6 ]

Reference： [1]Bulletin des Societes Chimiques Belges,1922,vol. 31,p. 176
Chemisches Zentralblatt,1923,vol. 94,p. 37

8
[ 107-93-7 ]
[ 625-68-3 ]
[ 300-85-6 ]

Reference： [1]Monatshefte fur Chemie,1929,vol. 53/54,p. 124

9
[ 25139-77-9 ]
furan-2,3,5(4H)-trione pyridine (1:1) [ No CAS ]
[ 107-93-7 ]
[ 300-85-6 ]

Reference： [1]Chemische Berichte,1909,vol. 42,p. 1221

10
[ 25139-77-9 ]
[ 300-85-6 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1911,vol. 383,p. 343
Chemisches Zentralblatt,1911,vol. 82,p. 442

11
[ 107-89-1 ]
[ 300-85-6 ]

Reference： [1]Patent: US2411700,1943,
[2]Patent: US2411700,1943,
[3]Patent: US2411700,1943,
[4]Patent: US2411700,1943,
[5]American Chemical Journal,1913,vol. 49,p. 183
[6]Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences,1873,vol. 76,p. 1166
Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences,1876,vol. 83,p. 255
[7]Patent: US2437410,1943,
[8]Patent: US2437410,1943,
[9]Patent: US2437410,1943,
[10]Patent: US2437410,1943,

12
[ 107-89-1 ]
[ 24621-61-2 ]
[ 300-85-6 ]

Reference： [1]Biochemische Zeitschrift,1926,vol. 174,p. 449

13
[ 541-50-4 ]
[ 300-85-6 ]

Reference： [1]Journal of Biological Chemistry,1948,vol. 176,p. 101

14
[ 5743-36-2 ]
[ 300-85-6 ]

Reference： [1]Journal of the Chemical Society,1928,p. 1424

15
[ 141-97-9 ]
[ 300-85-6 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1869,vol. 149,p. 207

16
[ 300-85-6 ]
[ 24621-61-2 ]

Reference： [1]Biochemische Zeitschrift,1928,vol. 200,p. 46,51

17
[ 300-85-6 ]
[ 6168-83-8 ]

Reference： [1]Journal of the Chemical Society,1903,vol. 83,p. 428

18
[ 300-85-6 ]
[ 625-72-9 ]

Reference： [1]Journal of the Chemical Society,1903,vol. 83,p. 428

21
[ 300-85-6 ]
[ 130-95-0 ]
[ 625-72-9 ]

Reference： [1]Journal of the Chemical Society,1902,vol. 81,p. 1403

22
[ 87400-71-3 ]
[ 300-85-6 ]

Reference： [1]Journal of general chemistry of the USSR,1962,vol. 32,p. 3635 - 3638
Zhurnal Obshchei Khimii,1962,vol. 32,p. 3707 - 3711

23
[ 108-24-7 ]
[ 300-85-6 ]
[ 5864-66-4 ]

Reference： [1]Journal of Organic Chemistry,1970,vol. 35,p. 2249 - 2253

24
[ 738-65-8 ]
[ 300-85-6 ]
1-(DL-3-Hydroxy-butanoyl>-1,3-bis-(4-dimethylamino-phenyl)-harnstoff [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1961,vol. 83,p. 4228 - 4233

25
[ 62631-17-8 ]
[ 300-85-6 ]
(S)-5-Benzyloxycarbonylamino-2-(3-hydroxy-butyrylamino)-pentanoic acid methyl ester [ No CAS ]

Reference： [1]Journal of the Chemical Society C: Organic,1971,p. 3743 - 3748

26
[ 186581-53-3 ]
[ 300-85-6 ]
[ 3976-69-0 ]

Reference： [1]Phytochemistry,1986,vol. 25,p. 2219 - 2222

27
[ 3068-88-0 ]
[ 3724-65-0 ]
[ 187737-37-7 ]
[ 124-38-9 ]
[ 300-85-6 ]

Reference： [1]Journal of Organic Chemistry,1989,vol. 54,p. 4596 - 4602

28
[ 108-24-7 ]
[ 300-85-6 ]
[ 52020-45-8 ]
[ 25654-45-9 ]

Reference： [1]Chemical and pharmaceutical bulletin,1985,vol. 33,p. 5258 - 5263

29
[ 132149-09-8 ]
[ 300-85-6 ]

Reference： [1]Tetrahedron Letters,1990,vol. 31,p. 5913 - 5916

30
[ 75-87-6 ]
[ 300-85-6 ]
[ 99902-27-9 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1990,vol. 63,p. 1898 - 1915

31
[ 75-77-4 ]
[ 300-85-6 ]
[ 108438-96-6 ]

Reference： [1]Journal of Organic Chemistry,1992,vol. 57,p. 6000 - 6002

32
[ 300-85-6 ]
[ 107-92-6 ]

Reference： [1]Synthesis,1991,p. 407 - 408

33
[ 124-38-9 ]
[ 75-56-9 ]
[ 300-85-6 ]

Reference： [1]Angewandte Chemie,1986,vol. 98,p. 629 - 631

34
[ 2443-40-5 ]
[ 300-85-6 ]
[ 600-15-7 ]

Reference： [1]Journal of Organic Chemistry,1981,vol. 46,p. 4655 - 4658
[2]Journal of Organic Chemistry,1981,vol. 46,p. 4655 - 4658
[3]Journal of Organic Chemistry,1981,vol. 46,p. 4655 - 4658

35
[ 1135-39-3 ]
[ 300-85-6 ]

Reference： [1]Tetrahedron Letters,1995,vol. 36,p. 31 - 34

36
[ 34837-55-3 ]
[ 300-85-6 ]
3-Hydroxy-selenobutyric acid Se-phenyl ester [ No CAS ]

Reference： [1]Tetrahedron Letters,1995,vol. 36,p. 31 - 34

37
[ 104-53-0 ]
[ 300-85-6 ]
(2S,6S)-6-Methyl-2-phenethyl-[1,3]dioxan-4-one [ No CAS ]
(2S,6R)-6-Methyl-2-phenethyl-[1,3]dioxan-4-one [ No CAS ]

Reference： [1]Tetrahedron Letters,1996,vol. 37,p. 141 - 144

38
[ 112-44-7 ]
[ 300-85-6 ]
(2S,6S)-2-Decyl-6-methyl-[1,3]dioxan-4-one [ No CAS ]
(2S,6R)-2-Decyl-6-methyl-[1,3]dioxan-4-one [ No CAS ]

Reference： [1]Tetrahedron Letters,1996,vol. 37,p. 141 - 144

39
[ 55265-82-2 ]
[ 300-85-6 ]

Reference： [1]Synthetic Communications,1998,vol. 28,p. 3057 - 3064

40
[ 110-85-0 ]
[ 999-97-3 ]
[ 300-85-6 ]
1-piperazin-1-yl-3-trimethylsilanyloxy-butan-1-one [ No CAS ]

Reference： [1]Tetrahedron Letters,1999,vol. 40,p. 3419 - 3422

41
[ 103-72-0 ]
[ 300-85-6 ]
6-methyl-3-phenyl-5,6-dihydro-1,3-oxazine-2,4(3H)-dione [ No CAS ]

Reference： [1]Heterocycles,1999,vol. 51,p. 2667 - 2673

42
[ 14152-97-7 ]
[ 300-85-6 ]
trans-but-2-enoic acid N-(2,'3',4',6'-tetra-O-acetyl-β-D-glucopyranosyl)amide [ No CAS ]

Reference： [1]Journal of Carbohydrate Chemistry,2000,vol. 19,p. 119 - 126

43
[ 300-85-6 ]
polyoxymethylene [ No CAS ]
[ 29269-86-1 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1902,vol. 21,p. 316

44
[ 3068-88-0 ]
[ 7732-18-5 ]
[ 300-85-6 ]

Reference： [1]Chemische Berichte,1915,vol. 48,p. 1264
Chemisches Zentralblatt,1916,vol. 87,p. 557

45
[ 3068-88-0 ]
alkali [ No CAS ]
[ 300-85-6 ]

Reference： [1]Chemische Berichte,1915,vol. 48,p. 1264
Chemisches Zentralblatt,1916,vol. 87,p. 557

46
[ 7653-39-6 ]
silver oxide [ No CAS ]
[ 300-85-6 ]

Reference： [1]Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences,1876,vol. 83,p. 256

47
[ 141-97-9 ]
sodium amalgam [ No CAS ]
[ 300-85-6 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1869,vol. 149,p. 207

53
[ 7664-93-9 ]
[ 300-85-6 ]
[ 3724-65-0 ]

Reference： [1]Chemische Berichte,1910,vol. 43,p. 578
Chemische Berichte,1902,vol. 35,p. 2576

54
[ 300-85-6 ]
diluted HClO₄ [ No CAS ]
[ 3724-65-0 ]

Reference： [1]Journal of the American Chemical Society,1939,vol. 61,p. 2272 - 2276
[2]Journal of the American Chemical Society,1939,vol. 61,p. 2272 - 2276
[3]Journal of the American Chemical Society,1939,vol. 61,p. 2272 - 2276

55
[ 75-07-0 ]
[ 300-85-6 ]
enzymesubstance from liver [ No CAS ]
coenzyme I [ No CAS ]
[ 64-17-5 ]
[ 541-50-4 ]

Reference： [1]Biochemical Journal,1931,vol. 31,p. 1081

56
[ 300-85-6 ]
[ 3724-65-0 ]
[ 7732-18-5 ]

Reference： [1]Zeitschrift fur Chemie,1869,p. 325

57
[ 300-85-6 ]
[ 1141-88-4 ]
Bis-(2-(3-hydroxy-butyrylamido)phenyl)-disulfide [ No CAS ]

Reference： [1]Patent: US6372802,2002,B1 .Location in patent: Example 4

58
[ 112-53-8 ]
[ 300-85-6 ]
dodecyl 3-Hydroxybutyrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With sulfuric acid;	EXAMPLE 10 Preparation of Dodecyl-3-Hydroxybutyrate A 500 ml one neck round bottom flask equipped with a Dean Stark trap, condenser and nitrogen inlet/outlet was charged with 72.0 g (0.69 moles) 3- hydroxybutyric acid, 268.5 g (1.45 moles) dodecyl alcohol, and 0.36 g sulfuric acid (based on 0.5 g/mole 3-hydroxybutyric acid). The mixture was heated to 115 degrees for 48 hours and water was collected as the reaction proceeded. The acid was neutralized by washing three times with 100 ml saturated sodium bicarbonate solution. The organic layer was collected and dried over magnesium sulfate. Excess dodecyl alcohol was removed by high vacuum distillation to yield 117.65 g (60% yield) of clear oil (91% pure by GC). GC (Rt, in minutes): 18.17. IR (neat, in cm-1): 3450 (br.s), 1730 (s), 1465 (s), 1375 (m), 1295 (s), 1180 (s), 1080 (m). 1 H NMR (200MHz, CDCl3 w/TMS): 4.15 (m, 1H), 4.1 (t, J=6.7Hz, 2H), 3.15 (br.s, --OH, 1H), 2.4 (apparent t, J=4Hz, 2H), 1.6 (br.m, 2H), 1.25 (br.s, 21H), 0.9 (br.t, J=6.8Hz, 3H).
91%	With sulfuric acid;	Preparation of Dodecyl 3-Hydroxybutyrate A 500 mL one neck round bottom flask equipped with a Dean Stark trap, condenser, and a nitrogen inlet/outlet was charged with 72.0 g (69 mmole) of 3-hydroxybutyric acid, 268.5 g (1.45 mole) of dodecyl alcohol, and 0.36 g of sulphuric acid. The mixture was heated to 120C for 48 ho and water was collected as the reaction proceeded. The ac was neutralized by washing three times with 100 mL saturat NaHCO3 solution. The organic layer was collected and drie over MgSO4 and concentrated. Excess dodecanol was removed high vacuum distillation to yield 117.65% (60% yield) of clear oil (91% pure by GC). GC (Rt): 18.17 IR (neat, in cmmin1): 3450 (br.s), 1730 (s), 1465 (s), 1375 (m), 1295 (s), 1180 (s), 1080 (m) 1H NMR (200 MHz, CDCl3 with TMS) delta 4.15 (m, 1H), 4.1 (t, J 6.7 Hz, 2H), 3.15 (br.s, -OH, 1H), 2.4 (apparent t, J = 4 2H), 1.6 (br.m, 2H), 1.25 (br.s, 20H), 0.9 (bt. t, J = 6.8 Hz, 3H)

Reference： [1]Patent: US5260051,1993,A
[2]Patent: EP530866,1993,A1

59
[ 112-30-1 ]
[ 300-85-6 ]
[ 143894-92-2 ]

Yield	Reaction Conditions	Operation in experiment
58%	With sulfuric acid;	Preparation of Decyl 3-Hydroxybutyrate A 100 ml one neck round bottom flask equipped with a Dean Stark trap, condenser and nitrogen inlet/outlet was charged with 20.8 g (0.20 moles) 3-hydroxybutyric acid, 63.3 g (0.40 moles) decyl alcohol, and 0.1 g sulfuric acid (based on 0.5 g/mole 3-hydroxybutyric acid). The mixture was heated to 140 C. for 8 hours and water was collected as the reaction proceeded. The acid was neutralized by washing three times with 50 ml saturated sodium bicarbonate solution. Approximately 50 ml ether was needed to break the emulsion. The organic layer was collected and dried over magnesium sulfate. Excess decyl alcohol was removed by high vacuum distillation to yield 28.3 g (58% yield) of clear viscous colorless oil. According to GC the product is 89.4% pure. GC (Rt in minutes): 15.6. IR (neat, in cm-1): 3450 (br.s), 1730 (s), 1470 (s), 1170 (s). 1 H NMR (200 MHz, FT, CDCl3 TMS): delta4.3 (m, 1H), 4.2 (t, J=b.7 Hz, 2H), 3.5 (--OH,d,J=3.8 Hz, 1H), 2.4 (d, J=5.9 Hz, 2H), 1.9-1.5 (br.s, 21H), 0.9 (br.t, J=6.7 Hz, 3H). 13 C NMR (50 MHz, CDCl3 with TMS): 170.15, 62.14, 61.59, 40.42, 29.3, 26.93, 26.8, 26.71, 26.65, 25.96, 23.3, 20.08, 19.92, 11.48.

Reference： [1]Patent: US5260051,1993,A

60
[ 107-06-2 ]
[ 300-85-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium chloride; sulfuric acid; In methanol;	REFERENTIAL EXAMPLE 2 Synthesis of beta-hydroxybutanoic acid In a liquid comprising 36 ml of absolute methanol and 36 ml of anhydrous 1,2-dichloroethane was suspended 5 g of optically active poly-beta-hydroxybutyrate, and 1.1 ml of concentrated sulfuric acid was added to the suspension and the mixture was heated and refluxed for 57 hours. The mixture was cooled and a saturated aqueous solution of sodium chloride was added to the mixture. Then, the mixture was filtered through Celite. The filtrate was extracted with 70 ml of ethanol one time and with 20 ml of ethanol three times.

Reference： [1]Patent: US5124069,1992,A

61
[ 2613-23-2 ]
[ 300-85-6 ]
[ 111478-28-5 ]

Yield	Reaction Conditions	Operation in experiment
16.2 g (10.2%)	With sodium hydroxide; In water;	PREPARATION G1 3-(3-Chloro-4-fluorophenoxy)butyric Acid To a solution of 27.2 g (0.68 mol) sodium hydroxide in 272 ml water was added 100 g (0.68 mol) <strong>[2613-23-2]3-chloro-4-fluorophenol</strong>. The solution was warmed to reflux and 55.4 ml (0.68 mol) of beta-butyrolactone was added dropwise over a 1 hour period. The reaction was cooled to 23 C. and the pH brought to 7 with concentrated hydrochloric acid. The neutral solution was washed with 3150 ml diethyl ether to remove unreacted phenol and then acidified to pH 2 with concentrated hydrochloric acid, extracted with 150 ml 1,2-dichloroethane, dried over magnesium sulfate and concentrated in vacuo to 4.3 g of an oil which by nuclear magnetic resonance examination was composed of 44 mol percent product and 56% 3-hydroxybutyric acid. The original diethyl ether washes were extracted with 3150 ml saturated sodium bicarbonate. The combined bicarbonate solutions were extracted with 150 ml diethyl ether and then the pH was brought to 2 with concentrated hydrochloric acid. Extraction with diethyl ether, washing with brine and drying over magnesium sulfate and concentration in vacuo gave 16.2 g (10.2%) of title product as an oil. 1 H-NMR(CDCl3)delta(ppm): 10.58 (broad s, 1H), 7.23-6.50 (m, 3H), 4.67 (m, 1H), 2.67 (m, 2H), 1.37 (d, 3H).
16.2 g (10.2%)	With sodium hydroxide; In water;	PREPARATION G1 3-(3-Chloro-4-fluorophenoxy)butyric Acid To a solution of 27.2 g (0.68 mol) sodium hydroxide in 272 ml water was added 100 g (0.68 mol) <strong>[2613-23-2]3-chloro-4-fluorophenol</strong>. The solution was warmed to reflux and 55.4 ml (0.68 mol) of beta-butyrolactone was added dropwise over a 1 hour period. The reaction was cooled to 23C. and the pH brought to 7 with concentrated hydrochloric acid. The neutral solution was washed with 3 * 150 ml diethyl ether to remove unreacted phenol and then acidified to pH 2 with concentrated hydrochloric acid, extracted with 150 ml 1,2-dichloroethane, dried over magnesium sulfate and concentrated in vacuo to 4.3 g of an oil which by nuclear magnetic resonance examination was composed of 44 mol percent product and 56% 3-hydroxybutyric acid. The original diethyl ether washes were extracted with 3 * 150 ml saturated sodium bicarbonate. The combined bicarbonate solutions were extracted with 150 ml diethyl ether and then the pH was brought to 2 with concentrated hydrochloric acid. Extraction with diethyl ether, washing with brine and drying over magnesium sulfate and concentration in vacuo gave 16.2 g (10.2%) of title product as an oil. 1H-NMR(CDCl3)delta(ppm): 10.58 (broad s, 1H), 7.23-6.50 (m, 3H), 4.67 (m, 1H), 2.67 (m, 2H), 1.37 (d, 3H).

Reference： [1]Patent: US4853410,1989,A
[2]Patent: EP230379,1991,B1

62
[ 22118-09-8 ]
[ 300-85-6 ]
[ 148274-02-6 ]

Yield	Reaction Conditions	Operation in experiment
70%	With triethylamine; In diethyl ether;	EXAMPLE 4 Preparation of 3-(alpha-bromoacetoxy)butyric acid 5 g (0.048 mol) of 3-hydroxybutyric acid and 0.062 mol of bromoacetyl chloride were dissolved in 100 ml of diethyl ether. This solution was stirred in an ice bath, and while maintaining the solution at a level of not higher than 5C, 20 ml of diethyl ether containing 5.35 g (0.053 mol) of triethylamine was dropwise added over a period of 30 minutes. After the dropwise addition, the mixture was stirred at room temperature for 10 hours. Then, triethylamine hydrochloride was filtered off from the reaction solution, and the filtrate was washed three times with distilled water. The ether solution thereby obtained was dried over anhydrous sodium sulfate, and then diethyl ether was distilled off. As a result, a slightly yellow desired compound was obtained in a yield of 70%.

Reference： [1]Patent: EP522422,1993,A2

63
[ 14878-26-3 ]
[ 75-56-9 ]
[ 300-85-6 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1967,vol. 40,p. 1456 - 1481
[2]Gmelin Handbuch der Anorganischen Chemie,Gmelin Handbook: Co: Org.Verb.1, 1.1.4.5.2.1.1, page 115 - 118

64
[ 1174417-90-3 ]
[ 300-85-6 ]
[ 1174418-01-9 ]

Reference： [1]Chemical Communications,2009,p. 3583 - 3584

65
[ 830-09-1 ]
[ 300-85-6 ]
[ 733739-13-4 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 3 2-carboxy-1-methylethyl-4'-methoxycinnamate was synthesised according to reaction scheme (7) below. A 250-ML round-bottomed flask equipped with a reflux condenser was charged with 150 ML of DMSO and 9 g of 4-methoxycinnamic acid. 6 g of thionyl chloride was added into the flask in a nitrogen atmosphere and stirred. 5 g of 3-hydroxybutyric acid was slowly added into the mixture, heated slowly to about 60 C. while stirring it, and reacted for 5 hours.The reaction mixture was cooled to room temperature, and the reaction product was poured into excess distilled water to precipitate it.The resulting precipitates were filtered, washed several times with distilled water, and recrystallized using a solvent mixture of chloroform and ethanol to provide 8.5 g of 2-carboxy-1-methylethyl-4'-methoxycinnamate.

Reference： [1]Patent: US2004/158050,2004,A1 .Location in patent: Page 8

66
[ 1207632-14-1 ]
[ 300-85-6 ]
[ 1207633-32-6 ]

Yield	Reaction Conditions	Operation in experiment
48%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; water; at 20℃; for 18h;	102. rac-1-[6-(3-Fluoro-4-methoxybenzyl)-1,2,4,7-tetrahydro-3H-indolo[2,3- c][1 ,7]naphthyridin-3-yl]-3-hydroxybutan-1 -one; 6-(3-Fluoro-4-methoxybenzyl)-2,3,4,7-tetrahydro-1 H-indolo[2,3-c][1 ,7]naphthyridine (example 20) (181 mg) is suspended in dichloromethane (5 ml) and rac-3-hydroxybutanoic acid (104 mg), 1- hydroxybenzotriazole hydrate (230 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (192 mg) and triethylamine (347 mul) are added. The mixture is stirred for 18 h at room temperature. After that, dichloromethane (15 ml) and water (15 ml) are added, the organic phase is dried (MgSO4) and concentrated in vacuo. The crude product is purified by column chromatography (silica gel, eluting with dichloromethane / methanol 20:1 (v/v)) followed by preparative HPLC (C18, eluting with gradient acetonitrile / water) to obtain 108 mg (48%) of the title compound. 1H-NMR (300 MHz, CDCI3); delta = 1.20-1.31 (m, 3H), 2.41-2.58 (m, 1 H), 2.61-2.69, 2.69-2.71 (2m, 1 H [rotamers]), 3.38-3.51 (m, 2H), 3.84, 3.85 (2s, 3H [rotamers]), 3.87-3.95, 4.02-4.18 (2m, 2H [rotamers]), 4.20-4.38 (m, 2H), 4.42 (s, 2H), 4.88, 5.05 (2s, 2H [rotamers]), 6.82-6.92 (m, 1 H), 6.92- 7.08 (m, 2H), 7.21-7.32 (m, 1 H), 7.40-7.58 (m, 2H), 7.98-8.15 (m, 2H). MS (MH+ found) = 448.2

Reference： [1]Patent: WO2010/15588,2010,A1 .Location in patent: Page/Page column 137

67
5-(methylsulfonyl)-1-[6-(piperidin-4-yloxy)pyrimidin-4-yl]indoline hydrochloride [ No CAS ]
[ 300-85-6 ]
[ 1145657-52-8 ]

Yield	Reaction Conditions	Operation in experiment
69%	With N-ethyl-N,N-diisopropylamine; 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride; In ethanol; at 20℃; for 72h;	Diisopropylethylamine (178 muL, 0.997 mmol) and (2-fluoroethyl) chloroformate (33 muL, 0.350 mmol) were added at 0C to a dichloromethane (2 mL) suspension of the 5-(methylsulfonyl)-1-[6-(piperidin-4-yloxy)pyrimidin-4-yl]indoline hydrochloride (188 mg, 0.396 mmol) produced in Reference Example 27, and the mixture was stirred at room temperature for 80 minutes. To the reaction solution, water was added, followed by extraction with ethyl acetate three times. The obtained organic layer was washed with water and saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [(i) hexane:dichloromethane=1:1, V/V; (ii) hexane:ethyl acetate:dichloromethane=2:1:2-1:1:1-2:2:1, V/V; (iii) ethyl acetate:dichloromethane=1:1, V/V] to obtain the title compound as white powder (58.8 mg, yield: 38%). 1H-NMR (400 MHz, CDCl3) delta ppm: 8.58 (1H, d, J = 9 Hz), 8.51 (1H, d, J = 1 Hz), 7.79 (1H, dd, J = 9 Hz, 2 Hz), 7.72 (1H, d, J = 2 Hz), 5.99 (1H, d, J = 1 Hz), 5.38-5.35 (1H, m), 4.70-4.68 (1H, m), 4.58-4.56 (1H, m), 4.40-4.38 (1H, m), 4.33-4.31 (1H, m), 4.07 (2H, t, J = 9 Hz), 3.88-3.82 (2H, m), 3.44-3.38 (2H, m), 3.32 (2H, t, J = 9 Hz), 3.04 (3H, s), 2.06-2.00 (2H, m), 1.82-1.74 (2H, m); MS (ESI) m/z: 465 [M + H]+.

Reference： [1]Patent: EP2210886,2010,A1 .Location in patent: Page/Page column 50

68
[ 186581-53-3 ]
[ 300-85-6 ]
[ 53562-86-0 ]
[ 3976-69-0 ]

Reference： [1]Journal of Natural Products,2010,vol. 73,p. 1350 - 1354

69
C₁₀H₁₇NO₆ [ No CAS ]
[ 300-85-6 ]

Reference： [1]Journal of Natural Products,2010,vol. 73,p. 1350 - 1354

70
poly(3-hydroxybutyrate) [ No CAS ]
[ 300-85-6 ]

Reference： [1]Journal of Molecular Catalysis B: Enzymatic,2011,vol. 71,p. 22 - 28

71
[ 3886-69-9 ]
[ 40138-16-7 ]
[ 300-85-6 ]
[ 1363311-69-6 ]

Reference： [1]Journal of Organic Chemistry,2012,vol. 77,p. 648 - 651

72
[ 25561-30-2 ]
[ 300-85-6 ]
C₇H₁₆O₃Si [ No CAS ]

Reference： [1]Central European Journal of Chemistry,2011,vol. 9,p. 813 - 824

73
[ 300-85-6 ]
[ 100-51-6 ]
[ 1135-39-3 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 4910 - 4913,4

74
[ 100-39-0 ]
[ 300-85-6 ]
[ 1135-39-3 ]

Yield	Reaction Conditions	Operation in experiment
45%	With caesium carbonate; In tetrahydrofuran;Reflux; Sealed tube;	Example 1:Benzyl protection of 3-hydroxybutanoic acid 1-Hydroxybutanoic acid 1 (434 mg, 4.17 mmol) was dissolved in THF (10 mL) and BnBr (700 mu,, 5.89 mmol) and CS2CO3 (2.5 g, 7.67 mmol) were added. The reaction mixture was refluxed in a sealed tube for 4-6 hours. After cooling down to room temperature the reaction mixture was filtrated and the residue was washed several times with EtOAc. The organic solvents were removed and the product was purified by automated flash chromatography on silica in one portion (SNAP 25 g cartridge, flow 30 ml/min, solvent A: DCM, solvent B: MeOH; gradient: 0 - 5 % B over 19 CV) to remove starting material and obtain desired benzyl protected 3-hydroxybutanoic acid 2 as yellow oil. Yield: 361 mg (45 %) MS: m/z 217.1 = [M+Na]+ (MW+Na calculated = 217.2).
45%	With caesium carbonate; In tetrahydrofuran;Reflux; Sealed tube;	Example 1: Benzyl protection of 3-hydroxybutanoic acid 1: 1 2 3-Hydroxybutanoic acid 1 (434 mg, 4.17 mmol) was dissolved in THF (10 mL) and BnBr (700 mu,, 5.89 mmol) and CS2CO3 (2.5 g, 7.67 mmol) were added. The reaction mixture was refluxed in a sealed tube for 4-6 hours. After cooling down to room temperature the reaction mixture was filtrated and the residue was washed several times with EtOAc. The organic solvents were removed and the product was purified by automated flash chromatography on silica in one portion (SNAP 25 g cartridge, flow 30 ml/min, solvent A: DCM, solvent B: MeOH; gradient: 0 - 5 % B over 19 CV) to remove starting material and obtain desired benzyl protected 3-hydroxybutanoic acid 2 as yellow oil. Yield: 361 mg (45 %) MS: m/z 217.1 = [M+Na]+ (MW+Na calculated = 217.2).
45%	With caesium carbonate; In tetrahydrofuran;Reflux; Sealed tube;	Example 1:Benzyl protection of 3-hydroxybutanoic acid 1: 3-Hydroxybutanoic acid 1 (434 mg, 4.17 mmol) was dissolved in THF (10 mL) and BnBr(700 iL, 5.89 mmol) and Cs2CO3 (2.5 g, 7.67 mmol) were added. The reaction mixture was refluxed in a sealed tube for 4-6 hours. After cooling down to room temperature the reaction mixture was filtrated and the residue was washed several times with EtOAc. The organic solvents were removed and the product was purified by automated flash chromatography on silica in one portion (SNAP 25 g cartridge, flow 30 mllmin, solvent A: CH2C12, solvent B:MeOH; gradient: 0 - 5 % B over 19 CV) to remove starting material and obtain desired benzyl protected 3-hydroxybutanoic acid 2 as yellow oil.Yield: 361 mg (45 %)MS: m/z 217.1 = [M+Na] (MW+Na calculated = 217.2).

45%	With caesium carbonate; In tetrahydrofuran;Sealed tube; Reflux;	3-Hydroxybutanoic acid 1 (434 mg, 4.17 mmol) was dissolved in THF (10 mL) and BnBr (700 muL, 5.89 mmol) and Cs2CO3 (2.5 g, 7.67 mmol) were added. The reaction mixture was refluxed in a sealed tube for 4-6 hours. After cooling down to room temperature the reaction mixture was filtrated and the residue was washed several times with EtOAc. The organic solvents were removed and the product was purified by automated flash chromatography on silica in one portion (SNAP 25 g cartridge, flow 30 ml/min, solvent A: DCM, solvent B: MeOH; gradient: 0-5% B over 19 CV) to remove starting material and obtain desired benzyl protected 3-hydroxybutanoic acid 2 as yellow oil. Yield: 361 mg (45%) MS: m/z 217.1=[M+Na]+ (MW+Na calculated=217.2).
45%	With caesium carbonate; In tetrahydrofuran;Sealed tube; Reflux;	3-Hydroxybutanoic acid 1 (434 mg, 4.17 mmol) was dissolved in THF (10 mL) and BnBr (700 muL, 5.89 mmol) and Cs2CO3 (2.5 g, 7.67 mmol) were added. The reaction mixture was refluxed in a sealed tube for 4-6 hours. After cooling down to room temperature the reaction mixture was filtrated and the residue was washed several times with EtOAc. The organic solvents were removed and the product was purified by automated flash chromatography on silica in one portion (SNAP 25 g cartridge, flow 30 ml/min, solvent A: DCM, solvent B: MeOH; gradient: 0-5% B over 19 CV) to remove starting material and obtain desired benzyl protected 3-hydroxybutanoic acid 2 as yellow oil. Yield: 361 mg (45%) MS: m/z 217.1=[M+Na]+ (MW+Na calculated=217.2).
45%	With caesium carbonate; In tetrahydrofuran;Sealed tube; Reflux;	3-Hydroxybutanoic acid 1 (434 mg, 4.17 mmol) was dissolved in THF (10 mL) and BnBr (700 muL, 5.89 mmol) and Cs2CO3 (2.5 g, 7.67 mmol) were added. The reaction mixture was refluxed in a sealed tube for 4-6 hours. After cooling down to room temperature the reaction mixture was filtrated and the residue was washed several times with EtOAc. The organic solvents were removed and the product was purified by automated flash chromatography on silica in one portion (SNAP 25 g cartridge, flow 30 ml/min, solvent A: CH2Cl2, solvent B: MeOH; gradient: 0 - 5 % B over 19 CV) to remove starting material and obtain desired benzyl protected 3-hydroxybutanoic acid 2 as yellow oil. Yield: 361 mg (45 %) MS: m/z 217.1 = [M+Na]+ (MW+Na calculated = 217.2).

Reference： [1]Patent: WO2013/24051,2013,A1 .Location in patent: Page/Page column 87
[2]Patent: WO2013/24052,2013,A1 .Location in patent: Page/Page column 119; 120
[3]Patent: WO2013/24053,2013,A1 .Location in patent: Page/Page column 84
[4]Patent: US9561287,2017,B2 .Location in patent: Page/Page column 95; 96
[5]Patent: US9872864,2018,B2 .Location in patent: Page/Page column 63; 64
[6]Patent: EP3643306,2020,A2 .Location in patent: Paragraph 0267-0268

75
[ 4368-06-3 ]
[ 40482-53-9 ]
[ 300-85-6 ]

Yield	Reaction Conditions	Operation in experiment
	With bacterial isolate; In aq. phosphate buffer; at 25℃;pH 7.2;	General procedure: The procedure for large scale biotransformation of racemic 3-hydroxybutyronitrile was similar to the general procedure, with the exception of the use of potassium phosphate buffer (0.1 M, pH 7.0, 100 mL) containing 3-hydroxybutyronitrile (85.1 mg, 10 mM). The resulting aqueous solution was basified to pH 12 with aqueous NaOH (2 M) and extracted with ethyl acetate (3 × 100 mL). The aqueous solution was acidified using aqueous HCl (2 M) to pH 2 and extracted with ethyl acetate (3 × 100 mL), dried over MgSO4 and the solvent removed under vacuum. The crude product was subjected to silica gel column chromatography eluted with a mixture of hexane and ethyl acetate (1:1) to give 3-hydroxybutyric acid in 42% yield (44 mg, 4.23 mmol) as clear oil. The configuration of the corresponding acid was determined by comparing the direction of specific rotation with that of an authentic sample. Enantiomeric excess values were obtained from HPLC analysis using a column of chiral stationary phase and correlated with literature. (R)-enantiomer elutes at 11.94 min, (S)-enantiomer elutes at 12.34 min [34]. 1H NMR (400 MHz, CDCl3) delta = 4.19-4.27 (1H, m), delta = 2.45-2.58 (2H, m), delta = 1.23 (3H, d, J = 6.3 Hz). 13C NMR (400 MHz, CDCl3) delta = 117, 76, 64, 42, 22 [alpha]d25 = +4.0 (c = 2.5, MeOH), and compared with that in the literature [alpha]d25 = +4.1 (c = 2.7, MeOH) [35]. This experiment was performed in triplicate.

Reference： [1]Journal of Molecular Catalysis B: Enzymatic,2013,vol. 97,p. 150 - 155

76
[ 6236-09-5 ]
[ 300-85-6 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 4228 - 4231

77
[ 18826-95-4 ]
[ 590-90-9 ]
[ 300-85-6 ]

Yield	Reaction Conditions	Operation in experiment
	With Au-Pd/carbon catalyst; oxygen; In water; at 100℃; under 2250.23 Torr; for 24h;	General procedure: Reactions were carried out using a Radley?s low pressure glass reactor (50 ml). A butanediol in water (20 ml, 0.6 M) and the catalyst(butanediol/metal ratio2000) were added into the reactor,which was then pressurized with oxygen (3 bar). The reaction mixture was heated to 100 C for 24 h under constant stirring(1000 rpm), then cooled to room temperature and analyzed. 1H-NMR spectroscopy was used for product identification; spectrawere acquired over a 16 scan period using a Bruker 400 MHz DPXsystem with a 5 mm auto tune broadband probe. All samples were prepared as dilute solutions in D2O. Carbon mass balances were calculated and were between 96 and 104%. Blank reactions have also been carried out with no oxidation activity detected in the absence of catalyst or with the KB-B carbon support.

Reference： [1]Tetrahedron,2014,p. 6055 - 6058

78
[ 18826-95-4 ]
[ 590-90-9 ]
[ 300-85-6 ]
[ 123-73-9 ]

Yield	Reaction Conditions	Operation in experiment
	With 1% platinum on charcoal; oxygen; In water; at 100℃; under 2250.23 Torr; for 24h;	General procedure: Reactions were carried out using a Radley?s low pressure glass reactor (50 ml). A butanediol in water (20 ml, 0.6 M) and the catalyst(butanediol/metal ratio2000) were added into the reactor,which was then pressurized with oxygen (3 bar). The reaction mixture was heated to 100 C for 24 h under constant stirring(1000 rpm), then cooled to room temperature and analyzed. 1H-NMR spectroscopy was used for product identification; spectrawere acquired over a 16 scan period using a Bruker 400 MHz DPXsystem with a 5 mm auto tune broadband probe. All samples were prepared as dilute solutions in D2O. Carbon mass balances were calculated and were between 96 and 104%. Blank reactions have also been carried out with no oxidation activity detected in the absence of catalyst or with the KB-B carbon support.
	With oxygen; In water; at 100℃; under 2250.23 Torr; for 24h;	General procedure: Reactions were carried out using a Radley?s low pressure glass reactor (50 ml). A butanediol in water (20 ml, 0.6 M) and the catalyst(butanediol/metal ratio2000) were added into the reactor,which was then pressurized with oxygen (3 bar). The reaction mixture was heated to 100 C for 24 h under constant stirring(1000 rpm), then cooled to room temperature and analyzed. 1H-NMR spectroscopy was used for product identification; spectrawere acquired over a 16 scan period using a Bruker 400 MHz DPXsystem with a 5 mm auto tune broadband probe. All samples were prepared as dilute solutions in D2O. Carbon mass balances were calculated and were between 96 and 104%. Blank reactions have also been carried out with no oxidation activity detected in the absence of catalyst or with the KB-B carbon support.
10%Spectr.; 42%Spectr.; 47%Spectr.	With oxygen; In water; at 100℃; under 2250.23 Torr; for 24h;	General procedure: (0017) Reactions were carried out using a Radley's low pressure glass reactor (50ml). A butanediol in water (20ml, 0.6M) and the catalyst (butanediol/metal ratio=2000) were added into the reactor, which was then pressurized with oxygen (3bar). The reaction mixture was heated to 100C for 24h under constant stirring (1000rpm), then cooled to room temperature and analyzed. 1H NMR spectroscopy was used for product identification; spectra were acquired over a 16 scan period using a Bruker 400MHz DPX system with a 5mm auto tune broadband probe. All samples were prepared as dilute solutions in D2O. Carbon mass balances were calculated and were between 96 and 104%. Blank reactions have also been carried out with no oxidation activity detected in the absence of catalyst or with the KB-B carbon support.

Reference： [1]Tetrahedron,2014,p. 6055 - 6058
[2]Tetrahedron,2014,p. 6055 - 6058
[3]Tetrahedron,2014,vol. 70,p. 6055 - 6058

79
ethyl 6-isopropoxy-1,4-dioxo-1,4-dihydronaphthalene-2-carboxylate [ No CAS ]
[ 300-85-6 ]
7-isopropoxy-3-methyl-3,4-dihydro-1H-benzo[g]isochromene-1,5,10-trione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With ammonium peroxodisulfate; silver nitrate; In water; acetonitrile; at 80℃; for 0.0833333h;Darkness; Inert atmosphere;	To a stirred solution of quinone 18 (164 mg, 0.57 mmol) in MeCN (1.1 mL) was added AgNO3 (145 mg, 0.854 mmol) and 3-hydroxybutyric acid (0.5 mL, 5.7 mmol) with light excluded. The reaction mixture was heated to 80 C and water (0.6 mL) added, immediately followed by dropwise addition of (NH4)2S2O8 (328 mg,1.1 mmol) in water (1.1 mL). The reaction mixture was stirred at 80 C for 5 min, then cooled to r.t. The reaction mixture was extracted with EtOAc (3 x 10 mL), the combined organic extracts dried over MgSO4, and concentrated in vacuo. Purification by flash column chromatography on silica (hexanes/EtOAc 3:2) afforded the title compound 20 as an orange solid (103 mg, 0.34 mmol, 60%). mp 88-92 C; IR numax (film): 2979, 1736, 1591, 1287, 1216, 1108 cm-1; 1H NMR (400 MHz, CDCl3) delta = 8.01 (d, J = 8.7 Hz, 1H), 7.41 (d, J = 2.6 Hz, 1H), 7.18 (dd, J = 8.7, 2.6 Hz, 1H), 4.71 (sep, J = 6.0 Hz, 1H), 4.65-4.56 (m, 1H), 3.14 (dd, J = 18.8 Hz, 3.1, Hz, 1H), 2.53 (dd, J = 18.8 Hz, 11.7 Hz, 1H), 1.52 (d, J = 6.3 Hz, 3H), 1.37 (d, J = 6.0 Hz,6H); 13C NMR (100 MHz, CDCl3) delta = 183.9, 178.7, 162.7, 160.2, 150.9, 133.2, 129.8, 128.4, 125.3, 122.6, 111.1, 73.9, 71.1, 29.0, 21.9, 20.6; HRMS (ESI) m/z calcd. for [C17H17O5]: 301.1071, found: 301.1074.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 87,p. 220 - 227

80
ethyl 6-isopropoxy-1,4-dioxo-1,4-dihydronaphthalene-2-carboxylate [ No CAS ]
[ 300-85-6 ]
7-isopropoxy-3-methyl-3,4-dihydro-1H-benzo[g]isochromene-1,5,10-trione [ No CAS ]
C₁₉H₂₂O₆ [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 87,p. 220 - 227

81
2-bromo-6-isopropoxynaphthalene-1,4-dione [ No CAS ]
[ 300-85-6 ]
2-bromo-3-(2-hydroxypropyl)-6-isoproxynaphthalene-1,4-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With ammonium peroxodisulfate; silver nitrate; In water; acetonitrile; at 80℃; for 0.416667h;Inert atmosphere;	To a stirred solution of bromoquinone 11 (470 mg, 1.6 mmol) in MeCN (3.2 mL) was added AgNO3 (320 mg, 1.9 mmol) and 3-hydroxybutyric acid (12) (0.44 mL, 4.8 mmol). The reaction mixture was heated to 80 C and water (1.6 mL) added, immediately followed by dropwise addition of (NH4)2S2O8 (910 mg, 3.2 mmol) in water (3.2 mL). The reaction was stirred at 80 C for 25 min, then cooled to r.t. The reaction mixture was extracted withEtOAc (3 10 mL), the combined organic extracts dried over MgSO4, and concentrated in vacuo. Purification by flash column chromatography on silica (hexanes/EtOAc 3:1) afforded the title compound 13 as an orange oil (400 mg, 1.1 mmol, 71%). IR nunmax (film): 2977, 2933, 1667, 1587, 1285, 1109 cm-1; 1H NMR (400 MHz,CDCl3) delta = 8.05 (d, J = 8.7 Hz, 1H), 7.48 (d, J = 2.6 Hz, 1H), 7.13 (dd,J = 8.7, 2.6 Hz, 1H), 4.73 (sep, J = 6.0 Hz, 1H), 4.21-4.13 (m, 1H), 3.09(dd, J = 12.7, 8.3 Hz, 1H), 2.98 (dd, J = 12.7, 4.4 Hz, 1H), 1.39 (d, J = 6.0 Hz, 6H), 1.34 (d, J = 6.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) delta = 183.1, 176.6, 163.1, 148.4, 141.3, 133.6, 130.3, 124.2, 121.7, 112.2,71.1, 67.5, 41.0, 24.4, 21.9; HRMS (ESI) m/z calcd. for [C16H18BrO4]: 353.0383, found: 353.0391.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 87,p. 220 - 227

82
[ 18162-48-6 ]
[ 300-85-6 ]
[ 107493-76-5 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; at 20℃;	3-Hydroxy-butyric acid (500 mg, 4.8 mmol) is dissolved in a mixture of TBSCl (1.5 g, 10.1 mmol) in dry DCM (48 mL). The resulting mixture is stirred overnight at room temperature. The resulting suspension is then filtered and the obtained residues are washed with DCM, then stirred in Et2O and filtered. The obtained filtrate is evaporated to give the desired product that is used as such.
	With 1H-imidazole; In dichloromethane; at 20℃;	3-Hydroxy-butyric acid (500 mg, 4.8 mmol) is dissolved in a mixture of TBSC1 (1.5 g, 10.1 mmol) in dry DCM (48 mL). The resulting mixture is stirred overnight at room temperature. The resulting suspension is then filtered and the obtained residues are washed with DCM, then stirred in Et20 and filtered. The obtained filtrate is evaporated to give the desired product that is used as such.

Reference： [1]Patent: US2015/45327,2015,A1 .Location in patent: Paragraph 0737-0738
[2]Patent: WO2015/18823,2015,A1 .Location in patent: Paragraph 00227

83
[ 5864-66-4 ]
[ 300-85-6 ]

Reference： [1]Advanced Synthesis and Catalysis,2015,vol. 357,p. 747 - 752

84
[ 6638-79-5 ]
[ 300-85-6 ]
[ 1313990-76-9 ]

Reference： [1]Advanced Synthesis and Catalysis,2015,vol. 357,p. 747 - 752

85
[ 18826-95-4 ]
[ 5077-67-8 ]
[ 300-85-6 ]

Yield	Reaction Conditions	Operation in experiment
39%Spectr.; 56%Spectr.	With oxygen; In water; at 100℃; under 2250.23 Torr; for 24h;	General procedure: (0017) Reactions were carried out using a Radley's low pressure glass reactor (50ml). A butanediol in water (20ml, 0.6M) and the catalyst (butanediol/metal ratio=2000) were added into the reactor, which was then pressurized with oxygen (3bar). The reaction mixture was heated to 100°C for 24h under constant stirring (1000rpm), then cooled to room temperature and analyzed. 1H NMR spectroscopy was used for product identification; spectra were acquired over a 16 scan period using a Bruker 400MHz DPX system with a 5mm auto tune broadband probe. All samples were prepared as dilute solutions in D2O. Carbon mass balances were calculated and were between 96 and 104percent. Blank reactions have also been carried out with no oxidation activity detected in the absence of catalyst or with the KB-B carbon support.
63%Spectr.; 35%Spectr.	With oxygen; In water; at 100℃; under 2250.23 Torr; for 24h;	General procedure: (0017) Reactions were carried out using a Radley's low pressure glass reactor (50ml). A butanediol in water (20ml, 0.6M) and the catalyst (butanediol/metal ratio=2000) were added into the reactor, which was then pressurized with oxygen (3bar). The reaction mixture was heated to 100°C for 24h under constant stirring (1000rpm), then cooled to room temperature and analyzed. 1H NMR spectroscopy was used for product identification; spectra were acquired over a 16 scan period using a Bruker 400MHz DPX system with a 5mm auto tune broadband probe. All samples were prepared as dilute solutions in D2O. Carbon mass balances were calculated and were between 96 and 104percent. Blank reactions have also been carried out with no oxidation activity detected in the absence of catalyst or with the KB-B carbon support.

Reference： [1]Tetrahedron,2014,vol. 70,p. 6055 - 6058
[2]Tetrahedron,2014,vol. 70,p. 6055 - 6058

86
6-(acetylamino)-4-hydroxy-3-[[4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-2-naphthalenesulfonic acid disodium salt [ No CAS ]
[ 2307-00-8 ]
[ 1119-48-8 ]
[ 927-83-3 ]
[ 84375-85-9 ]
[ 483-55-6 ]
[ 84-74-2 ]
[ 73712-25-1 ]
1-benzenesulfonyl piperidine-4-carboxylic acid allylamide [ No CAS ]
[ 79329-74-1 ]
[ 300-85-6 ]

Reference： [1]RSC Advances,2015,vol. 5,p. 10799 - 10808

87
6-(acetylamino)-4-hydroxy-3-[[4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-2-naphthalenesulfonic acid disodium salt [ No CAS ]
[ 1119-48-8 ]
[ 84375-85-9 ]
[ 84-74-2 ]
[ 300-85-6 ]

Reference： [1]RSC Advances,2015,vol. 5,p. 10799 - 10808

88
C_.I_. reactive red 2 [ No CAS ]
[ 872-50-4 ]
[ 1119-48-8 ]
[ 84-74-2 ]
[ 300-85-6 ]

Reference： [1]RSC Advances,2015,vol. 5,p. 10799 - 10808

89
[ 13324-20-4 ]
[ 1119-48-8 ]
[ 3156-73-8 ]
[ 84-74-2 ]
[ 300-85-6 ]
[ 619-55-6 ]

Reference： [1]RSC Advances,2015,vol. 5,p. 10799 - 10808

90
1-(piperidin-4-ylmethyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole [ No CAS ]
[ 300-85-6 ]
3-hydroxy-1-(4-((5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indol-1-yl)methyl)piperidin-1-yl)butan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine; In dichloromethane; at 20℃; for 16h;	Example 71 Synthesis of 3-hydroxy-1-(4-((5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indol-1-yl)methyl)piperidin-1-yl)butan-1-one To solution of 3-hydroxybutanoic acid (0.052 g, 0.49 mmol, 1.2 eq) in dichloromethane (5 mL, 10) was added BOP (0.273 g, 0.618 mmol, 1.5 eq) and triethylamine (168 L, 1.24 mmol, 3 eq) at room temperature. A solution of 1-(piperidin-4-ylmethyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole (0.150 g, 0.412 mmol, 1 eq)(prepared as described in example 31) in dichloromethane (10 mL) was then added and the mixture was stirred at room temperature for 16 h. After completion of the reaction (monitor by TLC, 5% MeOH-dichloromethane Rf=0.25), the mixture was poured into cold water and the organic layer was separated. The organic extract was washed with water followed by brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (100-200 mesh), eluting with a 70-80% gradient of ethyl acetate in hexanes to afford 3-hydroxy-1-(4-((5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indol-1-yl)methyl)piperidin-1-yl)butan-1-one (0.080 g, 43%) as a colorless, viscous liquid. LCMS (ES+): m/z 451.22 (M+H+); tr=1.88 min.

Reference： [1]Patent: US2015/252022,2015,A1 .Location in patent: Paragraph 0347; 0348

91
[ 167308-64-7 ]
[ 300-85-6 ]
(2R)-2,4-dihydroxy-N-{2-[(2-[(3S)-3-hydroxybutanoyl]sulfanyl}ethyl)carbamoyl]ethyl}-3,3-dimethylbutanamide [ No CAS ]
S-2-(3-[(R)-2,4-dihydroxy-3,3-dimethylbutyrylamino]propionylamino)ethyl (R)-3-hydroxybutanethioate [ No CAS ]

Reference： [1]Organic Letters,2015,vol. 17,p. 4452 - 4455

92
[ 100-46-9 ]
[ 300-85-6 ]
[ 89232-29-1 ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 10888 - 10894

93
Ac-Glu(tBu)-Thr(tBu)-Asp(tBu)-Lys-AMC [ No CAS ]
[ 300-85-6 ]
Ac-Glu-Thr-Asp-Lys((R/S)-3-hydroxybutyryl)-AMC [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 1021 - 1031

94
2-(1-(2-fluorophenyl)-1H-indazol-4-yl)hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one [ No CAS ]
[ 300-85-6 ]
2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-(3-hydroxybutanoyl)hexahydropyrrolo[3,4-c]pyrrol-1-(2H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In tetrahydrofuran; at 20℃; for 1.3h;	The product of Example 10A (0.10 g, 0.30 mmol), N-ethyl-N-isopropylpropan-2-amine (0.20 ml, 1.1 mmol), 3-hydroxybutyric acid (0.05 ml, 0.54 mmol) and dimethylamino-N,N'-dimethyl(3-oxido-1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)methaniminium hexafluorophosphate (HATU, 0.13 g, 0.35 mmol) in tetrahydrofuran (1.5 ml) were processed as described in Example 10B to give the title compound (0.051 g, 0.12 mmol, 40% yield). H1 NMR (500 MHz, methanol-d4) delta ppm 8.27-8.21(m, 1H), 7.63(t, J=7.4 Hz, 1H), 7.60-7.53(m, 1H), 7.53-7.48(m, 1H), 7.42(dd, J=15.8,8.2 Hz, 2H), 7.33-7.27(m, 1H), 7.27-7.21(m, 1H), 4.44-4.37(m, 1H), 4.26-4.19(m, 1H), 4.19-3.99(m, 2H), 3.96-3.71(m,2H), 3.69-3.35(m, 3H), 2.66-2.39(m, 2H), 1.29-1.22(m,3H); MS (ESI+) m/z 423 [M+H]+

Reference： [1]Patent: US2016/264582,2016,A1 .Location in patent: Paragraph 0327

95
[ 300-85-6 ]
[ 67-63-0 ]

Yield	Reaction Conditions	Operation in experiment
81%Chromat.	With Ru/CeO2; hydrogen; In water; at 160℃; under 22502.3 Torr; for 9h;Autoclave;	General procedure: Levulinic acid (LA) as a substrate was placed in a 50 mL stainless steel autoclave equipped with a Teflon (registered trademark) inner cylinder,1 mmol, catalyst (1) 100 mg [2 mol% of the substrate (in terms of metal)],And 3 mL of water were charged,The mixture was reacted under hydrogen pressure (3 MPa) at 150 C. for 12 hours to obtain a reaction product.Using a gas chromatograph mass spectrometer (GC-MS), conversion of raw materials(Conv. [%]) And the yield of each reaction product (yield [%]) were measured.

Reference： [1]Patent: JP2018/70523,2018,A .Location in patent: Paragraph 0060; 0070; 0071

96
[ 62-53-3 ]
[ 300-85-6 ]
[ 1954-91-2 ]

Reference： [1]Organic Letters,2018,vol. 20,p. 7371 - 7374

97
[ 156-43-4 ]
[ 300-85-6 ]
[ 1083-57-4 ]

Reference： [1]Organic Letters,2018,vol. 20,p. 7371 - 7374

98
[ 16874-17-2 ]
[ 300-85-6 ]
C₁₇H₂₅NO₄ [ No CAS ]

Reference： [1]Organic Letters,2018,vol. 20,p. 7371 - 7374

99
[ 1487-49-6 ]
[ 300-85-6 ]

Yield	Reaction Conditions	Operation in experiment
95%	With water; potassium hydroxide; at 45℃; for 24h;	300 g of water was added to the reaction vessel, and 150 g of 3-hydroxybutyrate or methyl 3-hydroxybutyrate was added thereto with stirring, and dissolved.156 g of potassium hydroxide was added, and then the temperature was raised to 45 C to carry out a constant reaction for 24 hours. After the reaction is completed, the water is distilled off at 40 C or lower, and the temperature is lowered to 0 C.Add isopropyl alcohol, stir well for 12 hours, and cool down to below 0 C for crystallization.And incubated at 0 C - 5 C for 24 hours, separated by suction filtration, washing the solid with ethanol,After drying at 55 C, 176 g of a 3-hydroxybutyric acid product was obtained in a yield of 95.1%.

Reference： [1]Patent: CN109369372,2019,A .Location in patent: Paragraph 0056-0058; 0060-0062; 0064-0066

100
[ 1190-73-4 ]
[ 300-85-6 ]
[ 166900-21-6 ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 1375 - 1378

101
[ 107-92-6 ]
[ 67-56-1 ]
[ 64-18-6 ]
[ 79-14-1 ]
[ 849585-22-4 ]
[ 591-81-1 ]
[ 110-15-6 ]
[ 75-07-0 ]
[ 64-19-7 ]
[ 67-64-1 ]
[ 300-85-6 ]
[ 600-15-7 ]

Reference： [1]Chemistry - A European Journal,2019,vol. 25,p. 10724 - 10734

102
[ 107-92-6 ]
[ 67-56-1 ]
[ 64-18-6 ]
[ 79-14-1 ]
[ 849585-22-4 ]
[ 591-81-1 ]
[ 75-07-0 ]
[ 64-19-7 ]
[ 67-64-1 ]
[ 300-85-6 ]
[ 600-15-7 ]

Reference： [1]Chemistry - A European Journal,2019,vol. 25,p. 10724 - 10734

103
C₁₆H₃₂N₂O₄ [ No CAS ]
[ 300-85-6 ]
C₁₆H₃₂N₂O₄*2C₄H₈O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In diethyl ether;	The bis leucine ester of 1 ,3-butanediol from above is dissolved in diethyl ether (1M) and to this solution is added a slight excess of 3-hydroxybutyric acid (2.1 equiv). The product precipitates out of the solution as a tan oil. The diethyl ether is then decanted from the reaction and the oil is triturated (rinsed and decanted) with ether 3 times. Trace solvent is then removed from the product by placing the oil on a high vacuum system for several hours.

Reference： [1]Patent: US2019/248733,2019,A1 .Location in patent: Paragraph 0030; 0034

104
[ 150-83-4 ]
[ 300-85-6 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In water;pH 2;	In a separate flask, (rac)-sodium 3-hydroxybutyrate is dissolved in a minimal amount of water and then the solution is acidified by addition of iN HC1 (aq) until the solution reaches a pH of 2.0. The aqueous solution is the extracted 3 times with equal volumes of ethet The ether solution is then dried over Na2504 and filtered. The ether solvent is then removed under reduced pressure on a rotary evaporator to give the 3-hydroxybutyric acid as a clear oil.

Reference： [1]Patent: US2019/248733,2019,A1 .Location in patent: Paragraph 0030; 0032

105
[ 72422-53-8 ]
[ 300-85-6 ]
C₁₈H₃₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41.7%	With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 45℃; for 21h;Inert atmosphere;	A flask was charged with 20.8 g of p-toluenesulfonic acid myristyl ester and 6.22 g of 3-hydroxybutyric acid (purity 99%, optical purity R-form 99% ee or higher), and purged with nitrogen. Then, 193 mL of dimethylformamide was added and stirred. Dissolved. Next, 23.45 g of potassium carbonate was added, and the mixture was stirred at room temperature for 17 hours. Furthermore, after stirring and reacting at 45 C. for 4 hours, the reaction solution was returned to room temperature, 500 mL of purified water and 120 mL of ethyl acetate were added, and the mixture was stirred for 30 minutes, and then separated. The aqueous layer was extracted 3 times with 150 mL of ethyl acetate, the organic layer was washed 5 times with 200 mL of purified water, and the entire organic layer was dried over magnesium sulfate. Magnesium sulfate was filtered off, and the obtained liquid was concentrated by an evaporator to obtain a waxy solid.The product was purified by column chromatography using hexane / ethyl acetate as a mobile phase to obtain a waxy solid (7.3 g; yield 41.7%). NMR analysis confirmed that the obtained waxy solid was a 3HB myristyl ester (Chemical Formula 3) having a structure represented by Chemical Formula 1 (n = 6) and contained no significant impurities.
41.7%	With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 45℃; for 21h;Inert atmosphere;	A flask was charged with 20.8 g of p-toluenesulfonic acid myristyl ester and 6.22 g of 3-hydroxybutyric acid (purity 99%, optical purity R-form 99% ee or higher), and purged with nitrogen. Then, 193 mL of dimethylformamide was added and stirred. Dissolved. Next, 23.45 g of potassium carbonate was added, and the mixture was stirred at room temperature for 17 hours. Furthermore, after stirring and reacting at 45 C. for 4 hours, the reaction solution was returned to room temperature, 500 mL of purified water and 120 mL of ethyl acetate were added, and the mixture was stirred for 30 minutes, and then separated. The aqueous layer was extracted 3 times with 150 mL of ethyl acetate, the organic layer was washed 5 times with 200 mL of purified water, and the entire organic layer was dried over magnesium sulfate. Magnesium sulfate was filtered off, and the obtained liquid was concentrated by an evaporator to obtain a waxy solid.The product was purified by column chromatography using hexane / ethyl acetate as a mobile phase to obtain a waxy solid (7.3 g; yield 41.7%). NMR analysis confirmed that the obtained waxy solid was a 3HB myristyl ester (Chemical Formula 3) having a structure represented by Chemical Formula 1 (C14) and contained no significant impurities.

Reference： [1]Patent: JP2019/178121,2019,A .Location in patent: Paragraph 0019-0021
[2]Patent: JP2019/178122,2019,A .Location in patent: Paragraph 0037-0039

106
[ 61954-92-5 ]
[ 300-85-6 ]
C₂₂H₄₄O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 45℃; for 21h;Inert atmosphere;	The flask was charged with 4.06 g of p-toluenesulfonic acid stearoyl ester and 2.74 g of 3-hydroxybutyric acid and purged with nitrogen, and then 100 mL of dimethylformamide was added and dissolved by stirring. Next, 3.96 g of potassium carbonate was added, and the mixture was stirred at room temperature for 17 hours. Furthermore, after stirring and reacting at 45 C. for 4 hours, the reaction solution was returned to room temperature, 250 mL of purified water and 100 mL of ethyl acetate were added, and the mixture was stirred for 30 minutes, and then separated. The aqueous layer was extracted 3 times with 100 mL of ethyl acetate, the organic layer was washed 3 times with 100 mL of purified water, and the entire organic layer was dried over magnesium sulfate. Magnesium sulfate was filtered off, and the obtained liquid was concentrated by an evaporator to obtain a waxy solid.The product was purified by column chromatography using hexane / ethyl acetate as a mobile phase to obtain a waxy solid (2.1 g; yield 62%). Wack obtained by NMR analysisIt was confirmed that the solid-like solid is a 3HB stearoyl ester having a structure represented by Chemical Formula 1 (n = 8) (Chemical Formula 4) and does not contain significant impurities.
62%	With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 45℃; for 21h;Inert atmosphere;	The flask was charged with 4.06 g of p-toluenesulfonic acid stearoyl ester and 2.74 g of 3-hydroxybutyric acid and purged with nitrogen, and then 100 mL of dimethylformamide was added and dissolved by stirring. Next, 3.96 g of potassium carbonate was added, and the mixture was stirred at room temperature for 17 hours. Furthermore, after stirring and reacting at 45 C. for 4 hours, the reaction solution was returned to room temperature, 250 mL of purified water and 100 mL of ethyl acetate were added, and the mixture was stirred for 30 minutes, and then separated. The aqueous layer was extracted 3 times with 100 mL of ethyl acetate, the organic layer was washed 3 times with 100 mL of purified water, and the whole organic layer was dried over magnesium sulfate. Magnesium sulfate was filtered off, and the obtained liquid was concentrated by an evaporator to obtain a waxy solid.The product was purified by column chromatography using hexane / ethyl acetate as a mobile phase to obtain a waxy solid (2.1 g; yield 62%). Wack obtained by NMR analysisIt was confirmed that the solid-like solid is a 3HB stearoyl ester (Chemical formula 4) having a structure represented by Chemical formula 4 (C18) does not contain significant impurities.

Reference： [1]Patent: JP2019/178121,2019,A .Location in patent: Paragraph 0023-0025
[2]Patent: JP2019/178122,2019,A .Location in patent: Paragraph 0041-0043

107
[ 6068-28-6 ]
[ 300-85-6 ]
C₂₀H₄₀O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87.2%	With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 45℃; for 21h;Inert atmosphere;	1.98 g of p-toluenesulfonic acid cetyl ester in the flaskandAfter charging 1.98 g of 3-hydroxybutyric acid (purity 99%, optical purity R-form 99% ee or higher) with nitrogen, 17 mL of dimethylformamide was added and dissolved by stirring. Next, 2.07 g of potassium carbonate was added, and the mixture was stirred at room temperature for 17 hours. Furthermore, the reaction was allowed to stir at 45 C for 4 hoursAfter that, the reaction solution was returned to room temperature, and 40 mL of purified water and 40 mL of ethyl acetate were added for 30 minutes.After stirring, the solution was separated. The aqueous layer was extracted 4 times with 10 mL of ethyl acetate, and the organic layer was purified with water 20The organic layer was washed 5 times with mL, and the whole organic layer was dried with magnesium sulfate. Filter off magnesium sulfateWhen the obtained liquid was concentrated by an evaporator, 1.58 g of a waxy solid was obtained..The product was purified by column chromatography using hexane / ethyl acetate as a mobile phase to obtain a waxy solid (1.43 g; yield 87.2%). NMR analysis confirmed that the obtained waxy solid was a 3HB cetyl ester (Chemical Formula 2) having a structure represented by Chemical Formula 1 (n = 7) and contained no significant impurities.
87.2%	With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 45℃; for 21h;Inert atmosphere;	A flask was charged with 1.98 g of p-toluenesulfonic acid cetyl ester and 1.43 g of 3-hydroxybutyric acid (purity 99%, optical purity R isomer 99% ee or more), and the atmosphere was purged with nitrogen. Then, 17 mL of dimethylformamide was added and stirred. Dissolved. Next, 2.07 g of potassium carbonate was added, and the mixture was stirred at room temperature for 17 hours. Furthermore, after stirring and reacting at 45 C. for 4 hours, the reaction solution was returned to room temperature, 40 mL of purified water and 40 mL of ethyl acetate were added, and the mixture was stirred for 30 minutes, and then separated. The aqueous layer was extracted 4 times with 10 mL of ethyl acetate, the organic layer was washed 5 times with 20 mL of purified water, and the entire organic layer was dried over magnesium sulfate. Magnesium sulfate was filtered off, and the obtained liquid was concentrated by an evaporator to obtain 1.58 g of a waxy solid.The product was purified by column chromatography using hexane / ethyl acetate as a mobile phase to obtain a waxy solid (1.43 g; yield 87.2%). NMR analysis (below) confirmed that the resulting waxy solid was 3HB cetyl ester (Chemical Formula 2) having the structure represented by Chemical Formula (C16) and contained no significant impurities.

Reference： [1]Patent: JP2019/178121,2019,A .Location in patent: Paragraph 0015-0017
[2]Patent: JP2019/178122,2019,A .Location in patent: Paragraph 0020-0022

108
C₄H₂Cl₂O₃ [ No CAS ]
[ 300-85-6 ]
3,3'-((2-oxosuccinyl)bis(oxy))dibutyric acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: OAA (1 equivalent) was dissolved in anhydrous dichloromethane (DCM) (0.1 M based off OAA) with a catalytic amount of dimethylformamide (DMF) (~l drop). Oxalyl chloride (2.5 equivalents) was added dropwise and the reaction was stirred at room temperature for 2 hours. The vial was evaporated to dryness to yield a yellow oil containing the diacyl chloride of OAA. In a separate vial, 2 equivalents of the appropriate alcohol (3 -hydroxy butanoic acid if synthesizing OAA(BHB)2 or propane- 1 ,2-diol if synthesizing OAAfPGf ) and NaH (2 equivalents) were suspended in DCM and stirred for 30 minutes. The diacyl chloride of OAA was redissolved in DCM and DMF and added dropwise to the vial containing the alcohol and NaH. The reaction was left to stir overnight, after which the solvent was evaporated to obtain the product.

Reference： [1]Patent: WO2020/69527,2020,A1 .Location in patent: Paragraph 0075-0076

109
[ 3724-65-0 ]
[ 300-85-6 ]
[ 107-92-6 ]

Reference： [1]Angewandte Chemie - International Edition,2020,vol. 59,p. 7456 - 7460
Angew. Chem.,2020,vol. 132,p. 7526 - 7530,5

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Technical Information

• Acids Combine with Acyl Halides to Produce Anhydrides • Acyl Chloride Hydrolysis • Add Hydrogen Cyanide to Aldehydes and Ketones to Produce Alcohols • Alcohol Syntheses from Aldehydes, Ketones and Organometallics • Alcohols are Weakly Basic • Alcohols as Acids • Alcohols Convert Acyl Chlorides into Esters • Alcohols from Haloalkanes by Acetate Substitution-Hydrolysis • Alcohols React with PX3 • Alcoholysis of Anhydrides • Aldehydes and Ketones Form Hemiacetals Reversibly • Aldol Addition • Alkene Hydration • Alkene Hydration • Amide Hydrolysis • Amide Hydrolysis • Anhydride Hydrolysis • Appel Reaction • Arndt-Eistert Homologation • Base-Catalyzed Hydration of α,β -Unsaturated Aldehydes and Ketones • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Carbonation of Organometallics • Carboxylate Salt Formation • Carboxylic Acids React with Alcohols to Form Esters • Chloroalkane Synthesis with SOCI2 • Chromium Reagents for Alcohol Oxidation • Chugaev Reaction • Claisen Condensations Produce β-Dicarbonyl Compounds • Claisen Condensations Produce β-Dicarbonyl Compounds • Convert Esters into Aldehydes Using a Milder Reducing Agent • Convert Haloalkanes into Alcohols by SN2 • Corey-Kim Oxidation • Decarboxylation of 3-Ketoacids Yields Ketones • Decarboxylation of Substituted Propanedioic • Decomposition of Lithium Aluminum Hydride by Protic Solvents • Deprotection of Cbz-Amino Acids • Dess-Martin Oxidation • Esters Are Reduced by LiAlH4 to Give Alcohols • Esters Hydrolyze to Carboxylic Acids and Alcohols • Ether Synthesis by Oxymercuration-Demercuration • Ethers Synthesis from Alcohols with Strong Acids • Formation of an Amide from an Amine and a Carboxylic Acid • Formation of an Amide from an Amine and a Carboxylic Acid • Friedel-Crafts Alkylations Using Alcohols • Geminal Diols and Acetals Can Be Hydrolyzed to Carbonyl Compounds • Grignard Reagents Transform Esters into Alcohols • Grignard Reagents Transform Esters into Alcohols • Haloalcohol Formation from an Alkene Through Electrophilic Addition • Halogen and Alcohols Add to Alkenes by Electrophilic Attack • Halogen and Alcohols Add to Alkenes by Electrophilic Attack • Heat of Combustion • Hemiaminal Formation from Amines and Aldehydes or Ketones • Hemiaminal Formation from Amines and Aldehydes or Ketones • HIO4 Oxidatively Degrades Vicinal Diols to Give Carbonyl Derivatives • Hunsdiecker-Borodin Reaction • Hydration of the Carbonyl Group • Hydride Reductions • Hydride Reductions of Aldehydes and Ketones to Alcohols • Hydride Reductions of Aldehydes and Ketones to Alcohols • Hydroboration-Oxidation • Hydroboration-Oxidation • Hydrolysis of Haloalkanes • Jones Oxidation • Ketones Undergo Mixed Claisen Reactions to Form β-Dicarbonyl Compounds • Martin's Sulfurane Dehydrating Reagent • Mitsunobu Reaction • Moffatt Oxidation • Nitriles Hydrolyze to Carboxylic Acids • Osmium Tetroxide Reacts with Alkenes to Give Vicinal Diols • Osmium TetroxideReacts with Alkenes to Give Vicinal Diols • Oxidation of Alcohols by DMSO • Oxidation of Aldehydes Furnishes Carboxylic Acids • Oxidation of Primary Alcohols Furnishes Carboxylic Acids • Oxymercuration-Demercuration • Passerini Reaction • Peptide Bond Formation with DCC • Periodic Acid Degradation of Sugars • Preparation of Alcohols • Preparation of Alkenes by Dehydration of Alcohols • Preparation of Alkenes by Dehydration of Alcohols • Preparation of Alkoxides with Alkyllithium • Preparation of Amines • Preparation of Carboxylic Acids • Primary Ether Cleavage with Strong Nucleophilic Acids • Reactions of Alcohols • Reactions of Amines • Reactions of Carboxylic Acids • Reactions with Organometallic Reagents • Reduction of an Ester to an Alcohol • Reduction of Carboxylic Acids by LiAlH4 • Reduction of Carboxylic Acids by Lithium Aluminum Hydride • Reduction of Carboxylic Acids by Lithium Aluminum Hydride • Ring Opening of an Oxacyclopropane by Lithium Aluminum Hydride • Ritter Reaction • Schmidt Reaction • Sharpless Olefin Synthesis • Specialized Acylation Reagents-Ketenes • Swern Oxidation • Synthesis of Alcohols from Tertiary Ethers • Synthesis of an Alkyl Sulfonate • The Conversion of Carboxylic Acids into Acyl Halides • The Nucleophilic Opening of Oxacyclopropanes • Thiazolium Salt Catalysis in Aldehyde Coupling • Thiazolium Salts Catalyze Aldehyde Coupling • Thiazolium Salts Catalyze Aldehyde Coupling • Transesterification • Ugi Reaction • Use 1,3-dithiane to Prepare of α-Hydroxyketones • Vicinal Anti Dihydroxylation of Alkenes • Williamson Ether Syntheses

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P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 300-85-6 ] {[proInfo.proName]}

Quality Control of [ 300-85-6 ]

Related Doc. of [ 300-85-6 ]

Product Details of [ 300-85-6 ]

Calculated chemistry of [ 300-85-6 ] Expand+

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 300-85-6 ]

Application In Synthesis of [ 300-85-6 ]

[ 300-85-6 ] Synthesis Path-Upstream 1~1

[ 300-85-6 ] Synthesis Path-Downstream 1~109

Technical Information

Related Functional Groups of [ 300-85-6 ]

Aliphatic Chain Hydrocarbons

Alcohols

Carboxylic Acids

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 300-85-6 ]