[ CAS No. 4630-80-2 ] {[proInfo.proName]}

Name: 4630-80-2|Methyl cyclopentanecarboxylate|97%
Brand: Ambeed
SKU: A543879
Price: 11.0 USD
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Quality Control of [ 4630-80-2 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 4630-80-2 ]

Product Details of [ 4630-80-2 ]

CAS No. :	4630-80-2	MDL No. :	MFCD00019290
Formula :	C₇H₁₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	IIHIJFJSXPDTNO-UHFFFAOYSA-N
M.W :	128.17	Pubchem ID :	78365
Synonyms :

Calculated chemistry of [ 4630-80-2 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.86
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	34.93
TPSA :	26.3 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.9 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.14
Log Po/w (XLOGP3) :	1.66
Log Po/w (WLOGP) :	1.35
Log Po/w (MLOGP) :	1.23
Log Po/w (SILICOS-IT) :	1.51
Consensus Log Po/w :	1.58

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.55
Solubility :	3.63 mg/ml ; 0.0283 mol/l
Class :	Very soluble
Log S (Ali) :	-1.83
Solubility :	1.91 mg/ml ; 0.0149 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.07
Solubility :	10.8 mg/ml ; 0.0843 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.43

Safety of [ 4630-80-2 ]

Signal Word:	Danger	Class:	3
Precautionary Statements:	P501-P240-P210-P233-P243-P241-P242-P280-P370+P378-P303+P361+P353-P403+P235	UN#:	3272
Hazard Statements:	H225	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 4630-80-2 ]

* 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 [ 4630-80-2 ]
Downstream synthetic route of [ 4630-80-2 ]

[ 4630-80-2 ] Synthesis Path-Upstream 1~20

1
[ 67-56-1 ]
[ 201230-82-2 ]
[ 142-29-0 ]
[ 25662-28-6 ]
[ 4630-80-2 ]
[ 120-92-3 ]

Reference： [1] Journal of Organic Chemistry, 2002, vol. 67, # 14, p. 5005 - 5008

2
[ 4630-80-2 ]
[ 25662-28-6 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1992, vol. 111, # 1, p. 1 - 15

3
[ 67-56-1 ]
[ 3400-45-1 ]
[ 4630-80-2 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 7 h; Stage #2: at 20℃; for 19 h;	To a solution of cyclopentanecarboxylic acid (9.5 mL, 87.6 mmol) in dry CH2Cl2 (100mL) in an oven-dried flask equipped with an anhydrous CaCl2 tube was added oxalylchloride (8.8 mL, 105.1 mmol) dropwise, followed by 2 drops of DMF. After 7 h, theresulting mixture was concentrated in vacuo and the residue was taken up with MeOH(25 mL). After 19 h, the mixture was concentrated in vacuo and the residue was dissolvedin CH2Cl2 (100 mL), then washed with saturated NaHCO3 and brine. The combinedorganic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo.The residue was purified by simple distillation to afford 2.8e (9.5 g, 74.3 mmol, 85 percentyield) as a colourless oil.

Reference： [1] Journal of Organic Chemistry, 1993, vol. 58, # 24, p. 6843 - 6850
[2] Synlett, 2017, vol. 28, # 13, p. 1570 - 1575
[3] Angewandte Chemie - International Edition, 2018, vol. 57, # 2, p. 574 - 578[4] Angew. Chem., 2018, vol. 130, p. 583 - 587,5
[5] Journal of the American Chemical Society, 1981, vol. 103, # 2, p. 436 - 442
[6] Journal of the American Chemical Society, 2013, vol. 135, # 7, p. 2635 - 2640
[7] Green Chemistry, 2017, vol. 19, # 22, p. 5396 - 5402
[8] Monatshefte fuer Chemie, 1937, vol. 70, p. 44,52
[9] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1982, p. 605 - 612
[10] Journal of Organic Chemistry, 1996, vol. 61, # 12, p. 3987 - 3995
[11] Patent: WO2012/25857, 2012, A1, . Location in patent: Page/Page column 67
[12] Patent: WO2017/107089, 2017, A1, . Location in patent: Page/Page column 34

4
[ 67-56-1 ]
[ 201230-82-2 ]
[ 142-29-0 ]
[ 25662-28-6 ]
[ 4630-80-2 ]
[ 120-92-3 ]

Reference： [1] Journal of Organic Chemistry, 2002, vol. 67, # 14, p. 5005 - 5008

5
[ 67-56-1 ]
[ 201230-82-2 ]
[ 142-29-0 ]
[ 4630-80-2 ]
[ 2258-56-2 ]
[ 39590-04-0 ]
[ 58101-60-3 ]

Reference： [1] Journal of Organic Chemistry, 2002, vol. 67, # 14, p. 5005 - 5008

6
[ 598-99-2 ]
[ 3400-45-1 ]
[ 4630-80-2 ]

Reference： [1] Synthetic Communications, 1984, vol. 14, # 1, p. 77 - 82

7
[ 186581-53-3 ]
[ 3400-45-1 ]
[ 4630-80-2 ]

Reference： [1] Journal of the Chemical Society. Perkin Transactions 2, 1997, # 12, p. 2787 - 2793
[2] Journal of Organic Chemistry, 1980, vol. 45, # 1, p. 43 - 47
[3] Patent: US4775692, 1988, A,

8
[ 67-56-1 ]
[ 201230-82-2 ]
[ 96-41-3 ]
[ 4630-80-2 ]

Reference： [1] Angewandte Chemie - International Edition, 2017, vol. 56, # 22, p. 6203 - 6207[2] Angew. Chem., 2017, vol. 129, p. 6299 - 6303,5

9
[ 14273-90-6 ]
[ 4630-80-2 ]

Reference： [1] Synthesis, 1977, p. 112 - 113

10
[ 292638-85-8 ]
[ 109-64-8 ]
[ 2396-80-7 ]
[ 4630-80-2 ]

Reference： [1] Journal of Organic Chemistry, 1990, vol. 55, # 8, p. 2503 - 2507

11
[ 67-56-1 ]
[ 64-18-6 ]
[ 142-29-0 ]
[ 4630-80-2 ]

Reference： [1] Journal of the American Chemical Society, 2018, vol. 140, # 15, p. 5217 - 5223

12
[ 627-31-6 ]
[ 292638-85-8 ]
[ 4630-80-2 ]

Reference： [1] Synthesis, 1975, p. 291 - 300

13
[ 56382-72-0 ]
[ 67-56-1 ]
[ 4630-80-2 ]

Reference： [1] Tetrahedron, 1977, vol. 33, p. 449 - 452

14
[ 35730-27-9 ]
[ 4630-80-2 ]

Reference： [1] Journal of the Chemical Society, 1959, p. 1761,1765

15
[ 20484-80-4 ]
[ 4630-80-2 ]

Reference： [1] Journal of the Chemical Society, 1959, p. 1761,1765

16
[ 67-56-1 ]
[ 3242-56-6 ]
[ 930-68-7 ]
[ 4630-80-2 ]
[ 108-94-1 ]
[ 120-92-3 ]

Reference： [1] Journal of Organic Chemistry, 1980, vol. 45, # 26, p. 5278 - 5283

17
[ 67-56-1 ]
[ 3242-56-6 ]
[ 930-68-7 ]
[ 7429-44-9 ]
[ 4630-80-2 ]
[ 108-94-1 ]

Reference： [1] Journal of Organic Chemistry, 1980, vol. 45, # 26, p. 5278 - 5283

18
[ 4630-80-2 ]
[ 32811-75-9 ]

Reference： [1] Science, 2010, vol. 327, # 5965, p. 533 - 571

19
[ 67-56-1 ]
[ 201230-82-2 ]
[ 142-29-0 ]
[ 4630-80-2 ]
[ 2258-56-2 ]
[ 39590-04-0 ]
[ 58101-60-3 ]

Reference： [1] Journal of Organic Chemistry, 2002, vol. 67, # 14, p. 5005 - 5008

20
[ 4630-80-2 ]
[ 220875-85-4 ]

Reference： [1] Bioorganic and medicinal chemistry letters, 2002, vol. 12, # 17, p. 2475 - 2478
[2] Chemistry - A European Journal, 2014, vol. 20, # 31, p. 9530 - 9533

[ 4630-80-2 ] Synthesis Path-Downstream 1~51

1
[ 67-56-1 ]
[ 3400-45-1 ]
[ 4630-80-2 ]

Yield	Reaction Conditions	Operation in experiment
85%		To a solution of cyclopentanecarboxylic acid (9.5 mL, 87.6 mmol) in dry CH2Cl2 (100mL) in an oven-dried flask equipped with an anhydrous CaCl2 tube was added oxalylchloride (8.8 mL, 105.1 mmol) dropwise, followed by 2 drops of DMF. After 7 h, theresulting mixture was concentrated in vacuo and the residue was taken up with MeOH(25 mL). After 19 h, the mixture was concentrated in vacuo and the residue was dissolvedin CH2Cl2 (100 mL), then washed with saturated NaHCO3 and brine. The combinedorganic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo.The residue was purified by simple distillation to afford 2.8e (9.5 g, 74.3 mmol, 85 %yield) as a colourless oil.
	sulfuric acid; for 48h;Reflux;	Step 1: Synthesis of methyl cyclopentanecarboxylate:OMeConcentrated H2S04 (19.1 ml, 1.0 eq) was added drop-wise to a solution of cyclopentanecarboxylic acid (25 g, 0.1953 mol) in MeOH (125 ml) at 0C and the reaction mixture was refluxed for about 48 hours. After completion of the reaction, the solvent was removed and the reaction mixture was dissolved in dichloromethane. The dichloromethane layer was washed with saturated NaHC03 solution and the organic layer was dried over anhydrous magnesium sulphate. The solvent was removed over rotary evaporator. The obtained residue with least moisture content was used directly for the next step. Yield: 16 gm.
	With sulfuric acid; at 75℃;	Into a 10-L,4-necked round-bottom flask,was placed cyclopentanecarboxylic acid (800 g,7.01 mol). This was followed by the addition of methanol (4 L),in portions. To this was added sulfuric acid (32 mL),in portions. The resulting solution was stined overnight at 75 C in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with water (4 L) and ether (2 L x 2). The organic layers were separated and combined,washed withaqueous sodium chloride (2 L),dried over anhydrous sodium sulfate and concentrated under vacuum to yleld the title compound.

Reference： [1]Journal of Organic Chemistry,1993,vol. 58,p. 6843 - 6850
[2]Synlett,2017,vol. 28,p. 1570 - 1575
[3]ChemMedChem,2019,vol. 14,p. 943 - 951
[4]Angewandte Chemie - International Edition,2018,vol. 57,p. 574 - 578
Angew. Chem.,2018,vol. 130,p. 583 - 587,5
[5]Journal of the American Chemical Society,1981,vol. 103,p. 436 - 442
[6]Journal of the American Chemical Society,2013,vol. 135,p. 2635 - 2640
[7]Green Chemistry,2017,vol. 19,p. 5396 - 5402
[8]Monatshefte fur Chemie,1937,vol. 70,p. 44,52
[9]Journal of the Chemical Society. Perkin transactions II,1982,p. 605 - 612
[10]Journal of Organic Chemistry,1996,vol. 61,p. 3987 - 3995
[11]Patent: WO2012/25857,2012,A1 .Location in patent: Page/Page column 67
[12]Patent: WO2017/107089,2017,A1 .Location in patent: Page/Page column 34

2
[ 75-77-4 ]
[ 4630-80-2 ]
[ 40195-25-3 ]

Reference： [1]Organic letters,2002,vol. 4,p. 4475 - 4478
[2]Angewandte Chemie - International Edition,2018,vol. 57,p. 2464 - 2468
Angew. Chem.,2018,vol. 130,p. 2489 - 2493,5
[3]Journal of Organometallic Chemistry,1972,vol. 46,p. 59 - 71
[4]Synthesis,1982,p. 58 - 60
[5]ACS Catalysis,2016,vol. 6,p. 3941 - 3945
[6]Angewandte Chemie - International Edition,2016,vol. 55,p. 8970 - 8974
Angew. Chem.,2016,vol. 128,p. 9116 - 9120,5
[7]Organic Letters,2019,vol. 21,p. 984 - 988

3
[ 110-52-1 ]
[ 4630-80-2 ]
[ 103724-63-6 ]

Yield	Reaction Conditions	Operation in experiment
48%	With n-butyllithium; ammonium chloride; diisopropylamine; In tetrahydrofuran;	Example 168 Preparation of 1-(4-Bromobutyl)cyclopentane Carboxylic Acid Methyl Ester To a solution of diisopropylamine (150 mmol, 21 mL) in THF (100 mL) was added dropwise a solution of n-butyl lithium (145 mmol, 58 mL, 2.5M) in hexanes at -10° C. while maintaining the temperature below 0° C. After addition, the solution was stirred for 30 min at 0° C. To this a solution of <strong>[4630-80-2]methyl cyclopentane carboxylate</strong> (100 mmol, 13.1 g) in THF (20 mL) was added dropwise at -70° C. maintaining the internal temperature between -60 to -70° C. After addition, the reaction mixture was stirred for 1 h at -50 to -60° C. Then, a solution of 1,4-dibromobutane (100 mmol, 21.59 g) in THF (20 mL) was added dropwise and the light brown suspension was stirred for 1 h at -60 to -70° C. Then, it was allowed to warm to room temperature and stirred overnight. The reaction mixture was poured into a saturated solution of ammonium chloride (200 mL) and the organic compound was extracted into ether (2*100 mL). The combined extracts were washed with a saturated brine solution (150 mL) and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solution was concentrated under vacuum and the resulting residue was distilled at 120-133° C./2.5 mm Hg to obtain 1-(4-bromobutyl)cyclopentane carboxylic acid methyl ester as a colorless oil (12.8 g, 48percent). HR MS (C11H19BrO2): Obs mass, a 262.0565. Calcd mass, 262.0568 (M+).

Reference： [1]Patent: US6455550,2002,B1
[2]Tetrahedron Letters,1986,vol. 27,p. 519 - 520
[3]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2475 - 2478

4
[ 865-50-9 ]
[ 4630-80-2 ]
[ 75621-26-0 ]

Reference： [1]Journal of the American Chemical Society,1981,vol. 103,p. 436 - 442

5
[ 4630-80-2 ]
[ 292638-85-8 ]
[ 121810-14-8 ]

Yield	Reaction Conditions	Operation in experiment
41%		Under nitrogen protection, -70 ° CDiisopropyl lithium tetrahydrofuran solution(22 mL, 22 mmol, 2M) was added THF (20 mL).<strong>[4630-80-2]Methyl cyclopentanecarboxylate</strong> (47A) at -70 °C(2.56 g, 20 mmol) dissolved in tetrahydrofuran (10 mL)Adding to the reaction solution, adding, and reacting at -70 ° C for 1 hour.Methyl acrylate (3.8 g, 44 mmol)Dissolved in tetrahydrofuran (10 mL) and added dropwise to the reaction solution.After the addition, the reaction was carried out at -70 ° C for 4 hours.Ammonium chloride solution (20 mL) was added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate (30 mL × 3).Column chromatography on crude material (petroleum ether/ethyl acetate (v/v) = 100:1 to 60:1)Obtaining an oily liquid dimethyl 6-oxaspiro[4.5]decane-7,9-dicarboxylate(47B)(4.2 g, yield: 41percent).

Reference： [1]Patent: CN109206417,2019,A .Location in patent: Paragraph 1565; 1568-1573
[2]Journal of Organic Chemistry,1989,vol. 54,p. 3514 - 3515

6
[ 4630-80-2 ]
[ 109-64-8 ]
[ 103724-62-5 ]

Yield	Reaction Conditions	Operation in experiment
	With diisopropylamine; In tetrahydrofuran; cyclohexane;	Example 170 Preparation of 1-(3-Bromopropyl)cyclopentane Carboxylic Acid Methyl Ester To a solution of 1.5 molar LDA in cyclohexane (60 mmol, 40 mL) cooled to -70° C. was added a solution of cyclopentane carboxylic acid methyl ester (42 mmol, 5.6 g) in THF (15 mL) over 30 min. The mixture was stirred for 1 hr at -70° C. Then a solution of 1,3-dibromopropane (60 mmol, 11.9 g) in THF (30 mL) which had been pre-cooled to -70° C. was added all at once and the reaction mixture was stirred at -70° C. for one hr then at room temperature overnight. The reaction mixture was poured into brine (200 mL), the layers were separated, the aqueous layer was extracted with ether (3*30 mL) and the combined organic layers were washed with brine (20 mL), dried (magnesium sulfate) and concentrated to give a yellow oil (15 g). Distillation through a short path apparatus with a 3" vigreux column gave a yellow oil, 7.96 g (76percent), bp 76-80° C. at 0.3 mm.

Reference： [1]Tetrahedron Letters,1986,vol. 27,p. 519 - 520
[2]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2475 - 2478
[3]Patent: US6455550,2002,B1

7
[ 4630-80-2 ]
[ 74-88-4 ]
[ 4630-83-5 ]

Yield	Reaction Conditions	Operation in experiment
85%		Add at -78 C under nitrogenn-BuLi (197 ml, 316 mmol, 1.6 M in hexanes)To containDiisopropylamine(53.1 ml, 373 mmol, 1.3 eq.) in 650 mL anhydrous THF.The mixture was stirred at the same temperature for 1 hour.And <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (36.8 g, 287 mmol) was added dropwise via an addition funnelA solution in 350 ml of anhydrous THF.The mixture was stirred at -78 C for 2 hours.Then, 30 ml of THF containing methyl iodide (26.8 ml, 431 mmol) was added dropwise.The temperature was maintained at -78 C for 1 hour and then slowly warmed to room temperature over 16 hours.The crude material was filtered through a short silica plug and the solvent was removed.The residue was diluted with diethyl ether (300 mL) and water (200 mL) and organics were extracted three times.The organic layer was washed with brine.It was dried over MgSO 4 .Most of the solvent was removed in vacuo and a white solid was filtered.The product is in the filtrate.Remove the solvent in a vacuum,Obtained methyl 1-methylcyclopentane-1-carboxylate as a colorless oil(34.5g, 85% yield),The product was used without further purification.
54%		A solution of cyclopentanecarboxylic acid methyl ester (78 mmol) in THF was added to a solution of freshly prepared LDA (78 mmol) in THF at -780C over 5 minutes. The mixture was warmed to O0C and stirred for 30 minutes at which point it was re-cooled to -780C. A solution of methyl iodide (78 mmol) in THF was then added and the mixture was allowed to come to room temperature and stirred overnight. NH4CI (sat. aq.) was added then the mixture was extracted with TBME. The organics were dried (MgSO4) then concentrated in vacuo to give a yellow oil. Column chromatography (silica gel, 1 - 15% EtOAc in heptane) gave the product as a clear oil (42 mmol, 54%).
		Step 1: Synthesis of methyl 1-methylcyclopentanecarboxylate:To a solution of di-isopropylamine (69 ml) in tetrahydrafuran (100 ml), n- BuLi (166 ml) in hexane was added at 0 C and the reaction mixture was allowed to stir at same temperature for about 10-15 minutes. The reaction mixture was stirred at room temperature for about 45 minutes. <strong>[4630-80-2]Methyl cyclopentanecarboxylate</strong> (25 g) in tetrahydrafuran (200 ml) was added drop-wise at -78 C to above reaction mixture. The reaction mixture was stirred at same temperature for about 2 hours and then methyl iodide was added drop-wise. The reaction was maintained at -78C for an hour and allowed to attain room temperature. The reaction mixture was stirred overnight at room temperature and quenched at 0 C with saturated aq. NH4C1 solution and the compound was extracted with ethyl acetate. The organic layer was washed with saturated brine solution, dried over anhydrous Na2S04 and concentrated. Crude product was directly used for the next step. 1H NMR (CDC13, 300 MHz): 3.66 (s, 3H), 2.10- 2.03 (m, 2H), 1.69- 1.64 (m, 4H), 1.50- 1.42 (m, 2H), 1.23 (s, 3H).

		Into a 10 L,4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen,was placed <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (400 g,3.12 mol) in a solutionof THf (4 L) at-78 C. To this was added LdA (3.12 L,) dropwise with stirring at-78 C. The resulting solution was stined for 1.5 h at-78 C before the dropwise addition of methyl iodide (1.33 L) at-78 C. The reaction was allowed to rest overnight and was then quenched by the addition of water (6 L). The resulting solution was partitioned with ether (2 L x 3) and the organic layers were combined. The resulting mixture was washed with aqueous sodium chloride (2 L),dried overanhydrous sodium sulfate and concentrated under vacuum. The crude product was purified by distillation under reduced pressure (0.01 mm Hg) and the fraction was collected at 120 C to yleld the title compound.
		To a solution of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (2.3 g, 17.95 mmol) in THF (10 mL) was added LDA (53.8 mmol) at -78 under N2protection in three-necked bottomed flask (100 mL) , the mixture was stirred at -78 for 1hs, then MeI (7.64 g, 53.8 mmol) was added and then stirred at -78 for 2hs, the resulting mixture was warmed up to 0 , quenched with NH4Cl solution (20 mL) , water (80 mL) was added, extracted with DCM (100 mL x 3) , combined organic layers , dried over Na2SO4, filtered and the filtrate was concentrated in vacuum to give the crude title compound.1HNMR (CDCl3, 400 MHz) delta: 3.68 (s, 3H) , 2.05-2.17 (m, 2H) , 1.64-1.74 (m, 4H) , 1.43-1.55 (m, 2H) , 1.25-1.26 (s, 3H) .
		To a solution of diisopropylamine (276 mL, 1.97 mol) in THF (400 mL) was added -BuLi (664 mL, 1.66 mol) at 0 C. The reaction mixture was stirred at this temperature for 15 min before warming to RT and aging for 45 min. The system was then cooled to -70 C and a solution of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (100 g, 780 mmol) in THF (800 mL) was added dropwise. After stirring for 2 h at this temperature, iodomethane (166 g, 1.18 mol) was added dropwise and the reaction mixture was stirred for an additional for 16 h. The mixture poured into aqueous NH4C1 and was extracted with EtOAc (2 x). The organic was washed with brine, dried and concentrated before distillation to obtain the title compound.

Reference： [1]Patent: CN109942636,2019,A .Location in patent: Paragraph 0266-0269
[2]Journal of the American Chemical Society,1981,vol. 103,p. 436 - 442
[3]Patent: WO2006/64286,2006,A1 .Location in patent: Page/Page column 28
[4]Tetrahedron,1985,vol. 41,p. 1267 - 1276
[5]Tetrahedron Letters,2007,vol. 48,p. 6343 - 6347
[6]Patent: WO2012/25857,2012,A1 .Location in patent: Page/Page column 49
[7]Patent: WO2017/107089,2017,A1 .Location in patent: Page/Page column 34; 41; 42
[8]Patent: WO2019/238,2019,A1 .Location in patent: Page/Page column 31
[9]Patent: WO2019/5587,2019,A1 .Location in patent: Page/Page column 30

8
[ 64394-45-2 ]
[ 4630-80-2 ]
[ 148256-86-4 ]

Reference： [1]Journal of Organic Chemistry,1996,vol. 61,p. 3987 - 3995

9
[ 6940-78-9 ]
[ 4630-80-2 ]
[ 182886-55-1 ]

Yield	Reaction Conditions	Operation in experiment
99%	With N,N,N,N,N,N-hexamethylphosphoric triamide; ammonium chloride; lithium diisopropyl amide;	Example 17 Production of 6-(benzoxazol-2-ylthio)-2,2-tetramethylene-N-(2,6-diisopropylphenyl)hexanamide: <strong>[4630-80-2]Methyl cyclopentanecarboxylate</strong> (1.3 g, 10 mmols) was gradually added to a tetrahyrofuran (THF) (10 ml) solution of lithium diisopropylamide (LDA) (11 mmols) at -78° C., and stirred for 30 minutes at said temperature. Then, still at said temperature, hexamethylphosphoramide (HMPA) (2.15 g, 12 mmols) and 1-bromo-4-chlorobutane (2.06 g, 12 mmols) were gradually added thereto in that order, and stirred for 2 hours still at -78° C. An aqueous saturated solution of ammonium chloride was added to the reaction mixture, which was then extracted with ether. The organic layer was washed with water and saturated saline in that order, and dried with anhydrous magnesium sulfate, and the solvent was evaporated. The residue was purified through silica gel column chromatography (developer: hexane/ether=10.1) to obtain 2.18 g (yield: 99percent) of methyl 6-chloro-2,2-tetramethylene-hexanoate as a colorless oil.
64%		Example 229 Preparation of Methyl 1-(4-chlorobutyl)cyclopentane Carboxylate 1-(4-Chlorobutyl)cyclopentane carboxylic acid methyl ester was prepared from cyclopentane carboxylic acid methyl ester and 4-chloro-1-bromobutane using the procedure described in example 7 to give a 64percent yield. HR MS (C11H19ClO2): Obs. mass, 218.1072. Calcd. mass, 218.1074, (M+).

Reference： [1]Patent: US6204278,2001,B1
[2]Tetrahedron Letters,2001,vol. 42,p. 8757 - 8760
[3]Patent: US6455550,2002,B1

10
[ 3210-08-0 ]
[ 4630-80-2 ]
Methyl 1-(4-hydroxybutyl)-1-cyclopentanecarboxylate [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2475 - 2478

11
[ 4630-80-2 ]
[ 4296-15-5 ]
[ 220875-96-7 ]

Reference： [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2475 - 2478

12
[ 4630-80-2 ]
[ 106-93-4 ]
[ 103724-64-7 ]

Yield	Reaction Conditions	Operation in experiment
80%		To a solution of diisopropylamine (396 mmol, 56 mL) in THF (85 mL) was added dropwise a solution of n-butyllithium (393 mmol, 240 mL, 1.6M) in hexanes at -10 C. while maintaining the temperature below 0 C. After addition, the solution was stirred for 30 min at 0 C. To this, a solution of cyclopentane carboxylic acid methyl ester (263 mmol, 37.4 g) in THF (50 mL) was added dropwise at -70 C. maintaining the internal temperature between -60 and -70 C. After addition, the reaction mixture was stirred for 1 h at -50 to -60 C. Then, a solution of 1,2-dibromoethane (545 mmol, 47 mL) in THF (50 mL) was added dropwise and the light brown suspension was stirred for 1 h at -70 to -60 C. Then, it was allowed to warm to RT and stirred overnight. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride (200 mL) and the organic compound was extracted into ether (2*100 mL). The combined extracts were washed with a saturated solution of sodium chloride (150 mL) and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solution was concentrated under vacuum and the resulting residue was distilled at 95-105 C./2.5 mm Hg to obtain 49.6 g (80% yield) of 1-(2-bromoethyl)cyclopentane carboxylic acid methyl ester as a colorless oil.
80%		Step 1: Preparation of 1-(2-bromoethyl)cyclopentanecarboxylic acid methyl ester (RO0276432) To a solution of diisopropylamine (396 mmol, 56 mL) in THF (85 mL) was added dropwise a solution of n-butyl lithium (393 mmol, 240 mL, 1.6M) in hexanes at -10 C. while maintaining the temperature below 0 C. After addition, the solution was stirred for 30 min at 0 C. To this, a solution of cyclopentanecarboxylic acid methyl ester (263 mmol, 37.4 g) in THF (50 mL) was added dropwise at -70 C. maintaining the internal temperature between -60 to -70 C. After addition, the reaction mixture was stirred for 1 h at -50 to -60 C. Then, a solution of 1,2-dibromoethane (545 mmol, 47 mL) in THF (50 mL) was added dropwise and the light brown suspension was stirred for 1 h at -70 to -60 C. Then, it was allowed to warm to room temperature and stirred overnight. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride (200 mL) and the organic compound was extracted into ether (2*100 mL). The combined extracts were washed with a saturated solution of sodium chloride (150 mL) and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solution was concentrated under vacuum and the resulting residue was distilled at 95-105 C./2.5 mm Hg to obtain 49.6 g (80% yield) of 1-[2-bromoethyl]cyclopentanecarboxylic acid methyl ester as a colorless oil.
80%		To a solution of diisopropylamine (56 mL, 396 mmol) in THF (85 mL) was added dropwise a solution of n-butyl lithium (240 mL, 393 mmol, 1.6M) in hexanes at -10 C while maintaining the temperature below 0 C. After addition, the solution was stirred for 30 mm at 0 C. To this, a solution of cyclopentanecarboxylic acid methyl ester (37.4 g, 263 mmol) in THF (50 mL) was added dropwise at -70 C maintaining the internal temperature between -60 to -70 C. Afteraddition, the reaction mixture was stirred for 1 h at -50 to -60 C. Then, a solution of 1,2- dibromoethane (47 mL, 545 mmol) in THF (50 mL) was added dropwise and the light brown suspension was stirred for 1 h at -70 to -60 C. Then, it was allowed to warm to room temperature and stirred overnight. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride (200 mL) and the organic compound was extracted into ether (2X 100 mL). The combined extracts were washed with a saturated solution of sodium chloride (150 mL) and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solution was concentrated under vacuum and the resulting residue was distilled at 95-105 C/2.5 mm Hg to obtain 49.6 g (80% yield) of 1-[2-bromoethyl]cyclopentanecarboxylic acid methyl ester as a colorless oil.

11.5 g (49%)

With n-butyllithium; sodium chloride; ammonium chloride; diisopropylamine; In tetrahydrofuran;

Example 176 Preparation of 1-(2-Bromoethyl)cyclopentane Carboxylic Acid Methyl Ester To a solution of diisopropylamine (150 mmol, 21 mL) in THF (100 mL) was added dropwise a solution of n-butyl lithium (145 mmol, 58 mL 2.5M) in hexanes at -10 C. while maintaining the temperature below 0 C. After addition, the solution was stirred for 30 min at 0 C. To this, a solution of cyclopentane carboxylic acid methyl ester (100 mmol 13.1 g) in THF (20 mL) was added dropwise at -70 C. maintaining the internal temperature between -60 to -70 C. After addition, the reaction mixture was stirred for 1 h at -50 to -60 C. Then, a solution of 1,2-dibromoethane (90 mmol, 16.91 g) in THF (20 mL) was added dropwise and the light brown suspension was stirred for 1 h at -60 to -70 C. Then, it was allowed to warm to room temperature and was stirred overnight. The reaction mixture was poured into a saturated solution of ammonium chloride (200 mL) and the organic compound was extracted into ether (2*100 mL). The combined extracts were washed with a saturated solution of sodium chloride (150 mL) and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solution was concentrated under vacuum and the resulting residue was distilled at 95-105 C./2.5 mm Hg to obtain 11.5 g (49%) of a colorless oil.

Reference： [1]Patent: US2013/79383,2013,A1 .Location in patent: Paragraph 0127-0128
[2]Patent: US2013/197205,2013,A1 .Location in patent: Paragraph 0184; 0185
[3]Patent: WO2013/110680,2013,A1 .Location in patent: Page/Page column 64
[4]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2475 - 2478
[5]Patent: US6455550,2002,B1

13
[ 67-56-1 ]
[ 201230-82-2 ]
[ 142-29-0 ]
[ 4630-80-2 ]
[ 2258-56-2 ]
[ 39590-04-0 ]
[ 58101-60-3 ]

Reference： [1]Journal of Organic Chemistry,2002,vol. 67,p. 5005 - 5008

14
[ 4630-80-2 ]
[ 40663-68-1 ]
[ 784148-89-6 ]

Yield	Reaction Conditions	Operation in experiment
97%	With lithium diisopropyl amide; In tetrahydrofuran; ethyl acetate;	Preparation c-4 Methyl 1-[[4-(allyloxy)phenyl](hydroxy)methyl]cyclopentanecarboxylate To a solution of methyl cyclopentanoate (3.84 g, 30.0 mmol), in tetrahydrofuran (30 mL) at -78° C. was added a solution of lithium diisopropylamide (15.0 mL of a 2M in tetrahydrofuran, 30.0 mmol) dropwise. The mixture was stirred for 2 hours and then 4-allyloxy benzaldehyde (2.12 g, 13.1 mmol) was added. The mixture was allowed to warm to ambient temperature and stirred for 18 hours. The mixture was diluted with water and extracted with ethyl acetate. The organic phase was washed with saturated aqueous sodium chloride and dried (anhydrous magnesium sulfate), filtered and evaporated. The residue was purified by flash column chromatography (hexanes to 50percent ethyl acetate/hexanes) to yield the title compound as a colorless oil (3.67 g, 97percent). LRMS (m/z): 273 (M-OH)+.
97%		To a solution of methyl cyclopentanoate (3. 84 g, 30. 0 MMOL), in tetrahydrofuran (30 mL) at-78 °C was added a solution of lithium DIISOPROPYLAMIDE (15. 0 mL of a 2M in tetrahydrofuran, 30. 0 MMOL) dropwise. The mixture was stirred for 2 hours and then 4-allyloxy benzaldehyde (2. 12 G, 13. 1 MMOL) was added. The mixture was allowed to warm to ambient temperature and stirred for 18 hours. The mixture was diluted with water and extracted with ethyl acetate. The organic phase was washed with saturated aqueous sodium chloride and dried (anhydrous magnesium sulfate), filtered and evaporated. The residue was purified by flash column chromatography (hexanes to 50percent ethyl acetate/hexanes) to yield the title compound as a colorless oil (3. 67 g, 97percent). LRMS (m/z) : 273 (M-OH) +.

Reference： [1]Patent: US2005/187266,2005,A1
[2]Patent: WO2004/92145,2004,A1 .Location in patent: Page 96-97

15
[ 4630-80-2 ]
[ 95882-33-0 ]

Yield	Reaction Conditions	Operation in experiment
		5-cyclopentyl-2H-pyrazol-3-amine used as a starting material was prepared as follows:; -To an argon flushed reaction vessel was added 1,4-dioxane (100 ml, anhydrous) and to this was added sodium hydride (3.60 g, 60percent dispersion in mineral oil, 90 mmoles). Acetonitrile (4.7 ml, 90 mmole, anhydrous) was added to the slurry and the mixture was stirred at room temperature for 30 mins. <strong>[4630-80-2]Methyl cyclopentanecarboxylate</strong> was added (9.6 g, 75 mmole) via syringe. The mixture was stirred at room temperature for 30 mins, then slowly heated to 105° C. overnight. The mixture was evaporated to dryness and the resulting solid dissolved in water (250 ml). The aqueous solution was extracted with DCM (3.x.75 ml). The aqueous layer was then acidified to pH 1-3 with concentrated hydrochloric acid (5-6 ml). The product was extracted into DCM (5.x.75 ml) and the combined organic extracts were dried over magnesium sulphate and filtered. The filtrate was evaporated at 600 mbar and 60° C. on a rotary evaporator, to avoid loss of any volatile product. The resulting oil was dissolved in ethanol (100 ml) and hydrazine hydrate (2 eq., 7.50 g, 150 mmoles) was added and the mixture was refluxed overnight. The solution was evaporated to dryness and then purified by silica column chromatography, eluting with a 0-10percent MeOH in DCM gradient to give the desired compound (7.6 g, 67percent)MS: m/z 152 (MH+)

Reference： [1]Patent: US2008/4302,2008,A1 .Location in patent: Page/Page column 52-53

16
[ 4630-80-2 ]
[ 6140-63-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: LDA / tetrahydrofuran / 2 h / 0 - 10 °C 2: LAH / CH₂Cl₂ / 16 h / -78 - 20 °C 3: PCC / CH₂Cl₂ / 16 h / 0 - 20 °C

Reference： [1]Arasappan, Ashok; Venkatraman, Srikanth; Padilla, Angela I.; Wu, Wanli; Meng, Tao; Jin, Yan; Wong, Jesse; Prongay, Andrew; Girijavallabhan, Viyyoor; George Njoroge [Tetrahedron Letters, 2007, vol. 48, # 36, p. 6343 - 6347]

17
[ 4630-80-2 ]
[ 38502-28-2 ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 6343 - 6347
[2]Journal of the American Chemical Society,1981,vol. 103,p. 436 - 442
[3]Patent: WO2017/107089,2017,A1
[4]Patent: WO2017/107089,2017,A1
[5]Patent: WO2012/25857,2012,A1
[6]Patent: WO2019/5587,2019,A1
[7]Patent: CN109942636,2019,A

18
[ 4630-80-2 ]
[ 220875-85-4 ]

Reference： [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 2475 - 2478
[2]Chemistry - A European Journal,2014,vol. 20,p. 9530 - 9533

19
[ 4630-80-2 ]
[ 1004-51-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) LDA, 2.) HMPA / 1.) THF, -78 deg C, 45 min, 2.) THF, RT, overnight 2: 81 percent / CoCl₂*6H₂O, NaBH₄ / tetrahydrofuran; H₂O / 48 h / Ambient temperature
	Multi-step reaction with 2 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -30 °C / Inert atmosphere 1.2: 3.5 h / -30 - 25 °C / Inert atmosphere 2.1: ammonium hydroxide; hydrogen / ethanol / 48 h / 25 °C

Reference： [1]Reddy, P. Amruta; Hsiang, Bonnie C. H.; Latifi, Tammy N.; Hill, Matthew W.; Woodward, Karen E.; Rothman, Steven M.; Ferrendelli, James A.; Covey, Douglas F. [Journal of Medicinal Chemistry, 1996, vol. 39, # 9, p. 1898 - 1906]
[2]Current Patent Assignee: ECCOGENE SHANGHAI - WO2021/83209, 2021, A1

20
[ 4630-80-2 ]
[ 13388-94-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1.) LDA / 1,) THF, -60 deg C to 25 deg C 2: NaI / acetone 3: 1.) ether/pentane, -100 deg C to -50 deg C, 45 min

Reference： [1]Does, T. van der; Klumpp, G. W.; Schakel, M. [Tetrahedron Letters, 1986, vol. 27, # 4, p. 519 - 520]

21
[ 4630-80-2 ]
[ 75-05-8 ]
[ 95882-33-0 ]

Yield	Reaction Conditions	Operation in experiment
94.4%		[0255j 3-cyclopentyl-3-oxopropanenitrile (JM2). To a dried, argon-charged roundbottom flask with large stir bar was added anhydrous tetrahydrofuran (160 ml), whichwas then cooled to -78° C before addition of 2.5 M n-Butyllithium in hexanes (64 mL, 160 mmol). Reaction was stirred for 5 minutes before addition of anhydrous acetonitrile (8.48 mL, 160 mmol) dropwise over 5 minutes. Reaction was stirred for 90 minutes at -78° C, followed by dropwise addition methylcyclopentane carboxylate (10.28 ml, 80.4 mmol) over 10 minutes. Reaction was allowed to stir for another 2 hours at -78° C, allowed to warm toroom temperature, and stirred for an additional 30 minutes. Reaction was quenched with 240 ml H20 and stirred until all solids dissolved. Aqueous layer was washed with ether (3x120 ml), and aqueous layer was slowly brought to pH 3.0 with dropwise addition of HC1, forming visible precipitate of product, which was extracted from aqueous with ether (3x 120 ml), dried with Mg504, filtered, and evaporated under reduced pressure to afford 10.4g (75.9 mmol,94.4percent yield) of a viscous yellow oil. Purity of product was sufficient to carry on to next step.LCMS (RT=1.35): 137.2 (100percent); 138.2 (10percent); 139.2 (3percent).
93%	With sodium hydride; In tetrahydrofuran; at 70℃; for 15h;	The 60percent sodium hydride 24.4g (0.61 muM) added to the 335 ml in tetrahydrofuran, heated to 75 °C. Cyclopentyl methyl formate 50g (0.39 muM) is dissolved in acetonitrile 25g (0.61 muM), slowly adding sodium hydride to the reaction solution. The completion of the dropping, 70 °C reaction 15 hours, cooling, concentrated in order to remove a portion of the solvent, adding water 180 ml, extracted with ethyl acetate three times, the organic phase is discarded. The aqueous phase is 4M hydrochloric acid to pH=2, extracted with ethyl acetate three times, drying, so as to obtain bright yellow 3 - cyclopentyl -3 - oxo third nitrile (II) 49.75g, yield is 93percent
91.2%	With sodium hydride; In tetrahydrofuran; mineral oil; at 70 - 75℃; for 15h;	NaH (2.75 g, 68.7 mmol, content 60percent) and 20 ml of THF were added to a 200 ml three-necked flask and the mixture was heated to 70-75° C. under heating, and methyl cyclopentanoate (8.00 g, 62.4 mmol) was added dropwise thereto. Anhydrous acetonitrile (15ml) solution, control system temperature at 70-75°C, reaction for 15h, then cooled to room temperature, add 50ml of ethyl acetate and 1N HCl solution, control system pH = 2-3, extract liquid, aqueous layer The mixture was extracted three times with ethyl acetate, and the organic layers were combined and dried by evaporation to obtain 2.42 g of a yellow oil (Compound II) with a yield of 91.2percent.

77%	With sodium hydride; In tetrahydrofuran; mineral oil; at 70℃;	To a suspension of sodium hydride (1.87 g, 55percent in mineral oil, 42.9 mmol) in THF (10 ml) was added a solution of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (5 g, 39.0 mmol) and acetonitrile (1.92 g, 2.45 ml, 46.8 mmol) in THF (3 ml) dropwise at 70°C. The mixture was heated to 70°C overnight, then cooled to room temperature, diluted with IN HCl and extracted with EtOAc. The combined organic layers were washed with water and brine, dried with Na2S04 and evaporated. The remaining residue was purified by column chromatography (silica gel, heptane/EtOAc 95:5 - 85: 15) to afford the title compound (4105 mg, 77percent) as light yellow liquid.
77%	With sodium hydride; In tetrahydrofuran; mineral oil; at 70℃;	Step A: 3-Cyclopentyl-3-oxo-propionitrile To a suspension of sodium hydride (1.87 g, 55percent in mineral oil, 42.9 mmol) in THF (10 ml) was added a solution of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (5 g, 39.0 mmol) and acetonitrile (1.92 g, 2.45 ml, 46.8 mmol) in THF (3 ml) dropwise at 70° C. The mixture was heated to 70° C. overnight, then cooled to room temperature, diluted with 1N HCl and extracted with EtOAc. The combined organic layers were washed with water and brine, dried with Na2SO4 and evaporated. The remaining residue was purified by column chromatography (silica gel, heptane/EtOAc 95:5-85:15) to afford the title compound (4105 mg, 77percent) as light yellow liquid.
	With sodium hydride; In tetrahydrofuran; at 70 - 72℃; for 16h;	To a suspension of NaH (2.75 g, 68.7 mmol) in THF (15 mL) at 70° C. was added dropwise a solution of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (8.00 g, 62.4 mmol) and anhydrous acetonitrile (3.91 mL, 74.9 mmol) in THF (5 mL). The mixture was stirred for 16 h at 70-72° C., cooled to rt, and diluted with ethyl acetate and aqueous HCl. The organic layer was washed with water and brine and dried (MgSO4). Removal of the solvent provided 3-cyclopentyl-3-oxopropanenitrile, which was used without further purification.
		To a suspension of NaH (2.75 g, 68.7 mmol) in THF (15 ml_) at 700C was added dropwise a solution of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (8.00 g, 62.4 mmol) and anhydrous acetonitrile (3.91 ml_, 74.9 mmol) in THF (5 ml_). The mixture was stirred for 16 h at 70°C-72°C, cooled to rt, and diluted with ethyl acetate and aqueous HCI. The organic layer was washed successively with water and brine and dried (MgSO4), filtered and concentrated under reduced pressure to provide the title compound, which was used without further purification.
	With sodium hydride; In tetrahydrofuran; at 70 - 72℃; for 16h;	To a suspension of NaH (2.75 G, 68.7 MMOL) in THF (15 mL) at 70°C was added dropwise a solution of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (8.00 g, 62.4 MMOL) and anhydrous ACETONITRILE (3.91 mL, 74.9 MMOL) in THF (5 mL). The mixture was stirred for 16 h at 70°C-72°C, cooled to rt, and diluted with ethyl acetate and aqueous HCI. The organic layer was washed with water and brine and dried (MGS04). Removal of the solvent provided 3-cyclopentyl-3-oxopropanenitrile, which was used without further purification.
	With potassium 2-methylbutan-2-olate; In tetrahydrofuran; toluene; at 0 - 20℃; for 78h;	General procedure: A solution of 1.02 mL (19.49 mmol) of acetonitrile in 13 mL of THF was cooled to 0° C and added 11.4 mL (19.49 mmol) of potassiumt-pentoxide solution (1.7 M in toluene) dropwise with constant stirring. The reaction mixture was stirred at room temperature for 2h. Reaction mixture was cooled again to 0° C and 1.32 g (9.74 mmol) of methyl benzoate was added dropwise followed by stirring for additional 2h at room temperature. After completion of the reaction (by TLC), crude mixture was quenched with 1NHCland extracted with ethyl acetate. The organic layer was washed with brine and dried over MgSO4. The crude was purified with column chromatography using hexane and ethyl acetate eluent to yield 0.56 g (40percent) 3-oxo-3-phenylpropanenitrile.

Reference： [1]Patent: WO2014/190207,2014,A1 .Location in patent: Paragraph 0255
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 1082 - 1105
[3]Patent: CN104496904,2017,B .Location in patent: Sheet 0058; 0059; 0060; 0061; 0069; 0070; 0079; 0080
[4]Patent: CN107674026,2018,A .Location in patent: Paragraph 0055; 0056; 0075; 0076; 0086; 0087
[5]Patent: WO2013/64465,2013,A1 .Location in patent: Page/Page column 168
[6]Patent: US2013/116234,2013,A1 .Location in patent: Paragraph 0938; 0939
[7]Beilstein Journal of Organic Chemistry,2019,vol. 15,p. 2930 - 2935
[8]Patent: US2005/192294,2005,A1 .Location in patent: Page/Page column 13
[9]Patent: WO2007/64872,2007,A2 .Location in patent: Page/Page column 73
[10]Patent: WO2004/50650,2004,A1 .Location in patent: Page 25-26
[11]European Journal of Medicinal Chemistry,2012,vol. 48,p. 1 - 15
[12]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 3736 - 3740

22
[ 75-11-6 ]
[ 4630-80-2 ]
[ 871021-95-3 ]

Yield	Reaction Conditions	Operation in experiment
52%		Step 1. Methyl 1-(iodomethyl)cyclopentanecarboxylate To a stirred solution of HN(iPr)2 (1.31 mL, 9.36 mmol) in THF (5 mL) was added n-BuLi (1.58 M in hexane, 5.43 mL, 8.58 mmol) with keeping -10° C. under N2, and the mixture was stirred at -10° C. for 1 h. Then, to this mixture was added a solution of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (1.00 g, 7.80 mmol) in THF (3 mL) dropwise at 0° C., and the mixture was stirred at 0° C. for 2 h. Finally, to this mixture was added CH2I2 (0.628 mL, 7.80 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with sat. NH4Cl aq. (50 mL), extracted with Et2O (75 mL) for two times, and the combined organic layer was washed with brine (75 mL). The organic layer was dried over Na2SO4, filtered and concentrated. Removal of the solvent gave a residue, which was chromatographed on a column of silica gel eluding with EtOAc/hexane (1:20-->1:10) to give 1.085 g (52percent) of title compound as a colorless oil. 1H-NMR (CDCl3) delta 3.73 (3H, s), 3.42 (2H, s), 2.30-2.15 (2H, m), 1.80-1.55 (6H, m).

Reference： [1]Patent: US2005/277671,2005,A1 .Location in patent: Page/Page column 27

23
[ 35354-37-1 ]
[ 4630-80-2 ]
methyl 1-(5-methylhexyl)cyclopentanecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%	With lithium hexamethyldisilazane; In tetrahydrofuran; water;	(a) Methyl 1-(5-methylhexyl)cyclopentanecarboxylate To a solution of methyl cyclopentanecarboxylate (300 mg, 2.3 mmol) in THF (20 ml) at -78° C. was added LHMDS (4.6 mL, 4.6 mmol) and stirred for 30 min, and followed by <strong>[35354-37-1]1-bromo-5-methylhexane</strong> (626 mg, 3.5 mmol). The mixture was stirred from -78° C. to rt over 16 hr, before 30 ml of H2O was added and then was extracted with CH2Cl2 (2*30 mL). The combined extracts were washed with water, dried over MgSO4, filtered and concentrated, then purified using flash chromatography to give an oil (110 mg, 21percent). MS [M+H]+333.

Reference： [1]Patent: US2002/61874,2002,A1

24
[ 5162-44-7 ]
[ 4630-80-2 ]
[ 220878-56-8 ]

Yield	Reaction Conditions	Operation in experiment
13.77 g (53%)	With n-butyllithium; sodium chloride; ammonium chloride; diisopropylamine; In tetrahydrofuran;	Example 230 Preparation of 1-(3-Butenyl)cyclopentane Carboxylic Acid Methyl Ester To a solution of diisopropylamine (225 mmol, 31.6 mL) in THF (150 mL) was added dropwise a solution of n-butyl lithium (217.5 mmol, 87 mL, 2.5M) in hexanes at -10° C. while maintaining the temperature below 0° C. After addition, the solution was stirred for 30 min at 0° C. To this, a solution of <strong>[4630-80-2]methyl cyclopentane carboxylate</strong> (150 mmol, 19.23 g) in THF (30 mL) was added dropwise at -70° C. maintaining the internal temperature between -60 to -70° C. After addition, the reaction mixture was stirred for 1 h at -50 to -60° C. Then, a solution of 4-bromo-1-butene (142.2 mmol, 19.2 g) in THF (30 mL) was added dropwise and the light brown suspension was stirred for 1 h at -60 to -70° C. Then, it was allowed to warm to room temperature and stirred overnight. The reaction mixture was poured into a saturated solution of ammonium chloride (250 mL) and the mixture was extracted with ether (2*150 mL). The combined extracts were washed with a saturated solution of sodium chloride (150 mL) and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solution was concentrated under vacuum and the residue was distilled at 63-67° C./2.5 mm Hg to give 13.77 g (53percent) of a colorless oil. HR MS (C11H16O2): Obs mass, 182.1311. Calcd mass, 182.1307 (M+).
		Intermediate (7)1 -(3-Oxo-prop -cyclopentanecarboxylic acid methyl esterStep 1 : 1 -But-3-enyl-cyclopentanecarboxylic acid methyl ester To a solution of diisopropylamine (10.5 mL, 75 mmol) in tetrahydrofuran (100 mL) pre-cooled to -75°C was added a 2.5 M solution of n-butyllithium in hexanes (30 mL, 75 mmol) dropwise. Following addition, the reaction mixture was warmed to 0°C for 30 min and then re-cooled to -75°C. To the mixture was added a solution of <strong>[4630-80-2]methyl cyclopentane carboxylate</strong> (8 g, 62 mmol) in tetrahydrofuran (40 mL) dropwise. After stirring for 30 min, a solution of 4-bromo-1 -butene (8.2 mL, 81 mmol) in HMPA (6 mL) was added dropwise. The cooling bath was removed to allow the mixture to warm to 20°C. After 1 .5 h, the reaction mixture was poured into ice/H2O (200 mL). The two layers were separated and the aqueous layer was extracted with Et2O (100 mL). The organic solutions were combined and dried over K2CO3, filtered and concentrated to afford the 12.1 g of the title compound as an oil.LC/MS: RT = 3.57 min. MS (ESI) m/z =183 (M+H+)
		Step l : 1 -But-3-enyl-cyclopentanecarboxylic acid methyl esterTo a solution of diisopropylamine (10.5 mL, 75 mmol) in tetrahydrofuran (100 mL) pre-cooled to -75°C was added a 2.5 M solution of n-butyllithium in hexanes (30 mL, 75 mmol) dropwise. Following addition, the reaction mixture was warmed to 0°C for 30 min and then re-cooled to -75°C. To the mixture was added a solution of <strong>[4630-80-2]methyl cyclopentane carboxylate</strong> (8 g, 62 mmol) in tetrahydrofuran (40 mL) dropwise. After stirring for 30 min, a solution of 4-bromo-1 -butene (8.2 mL, 81 mmol) in HMPA (6 mL) was added dropwise. The cooling bath was removed to allow the mixture to warm to 20°C. After 1 .5 h, the reaction mixture was poured into ice/H2O (200 mL). The two layers were separated and the aqueous layer was extracted with Et2O (100 mL). The organic layers were combined and dried over K2CO3, filtered and concentrated to afford the 12.1 g of the title compound as an oil.LCMS: LC RT = 3.57 min, MS (ESI): 183

-(3-Oxo-propyl)-cyclopentanecarboxylic acid methyl esterTo a solution of diisopropylamine (10.5 mL, 75 mmol) in tetrahydrofuran (100 mL) pre-cooled to -75°C was added a 2.5 M solution of n-butyllithium in hexanes (30 mL, 75 mmol) dropwise. Following addition, the reaction mixture was warmed to 0°C for 30 min and then re-cooled to -75°C. To the mixture was added a solution of <strong>[4630-80-2]methyl cyclopentane carboxylate</strong> (8 g, 62 mmol) in tetrahydrofuran (40 mL) dropwise. After stirring for 30 min, a solution of 4-bromo-1 -butene (8.2 mL, 81 mmol) in HMPA (6 mL) was added dropwise. The cooling bath was removed to allow the mixture to warm to 20°C. After 1 .5 h, the reaction mixture was poured into ice/H2O (200 mL). The two layers were separated and the aqueous layer was extracted with Et2O (100 mL). The organic solutions were combined and dried over K2CO3, filtered and concentrated to afford the 12.1 g of the title compound as an oil.LC RT = 3.57 min, MS (ESI): 183

Reference： [1]Patent: US6455550,2002,B1
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 2443 - 2463
[3]Patent: WO2011/143150,2011,A1 .Location in patent: Page/Page column 38-39
[4]Patent: WO2011/143148,2011,A1 .Location in patent: Page/Page column 30
[5]Patent: WO2011/143163,2011,A1 .Location in patent: Page/Page column 24

25
[ 709-63-7 ]
[ 4630-80-2 ]
1-Cyclopentyl-3-(4-trifluoromethylphenyl)-propane-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate;18-crown-6 ether; In tetrahydrofuran; 1-Cyclopentyl-3-(4-trifluoromethylphenyl)-propane-1,3-dione;	EXAMPLE XIV 1-Cyclopentyl-3-(4-trifluoromethylphenyl)-propane-1,3-dione STR52 1.97 kg of potassium tert-butoxide, 2.26 kg of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong>, 1.66 kg of p-trifluoromethylacetophenone and 36 g of 18-crown-6 ether were refluxed in 18 litres of tetrahydrofuran for 4 hours. Quenching of the reaction was carried out using 16 litres of 10percent strength hydrochloric acid at room temperature. The aqueous phase was extracted with ethyl acetate and the combined organic phases were washed with saturated sodium chloride solution. After distilling off the solvent, the residue was distilled in an oil-pump vacuum at 1.5 mbar. 1.664 kg of 1-cyclopentyl-3-(4-trifluoromethylphenyl)propane-1,3-dione resulted as an oil, which crystallized completely on allowing to stand. Boiling point: 138-145° C./1.5 mbar.
	With potassium tert-butylate;18-crown-6 ether; In tetrahydrofuran; 1-Cyclopentyl-3-(4-trifluoromethylphenyl)-propane-1,3-dione;	EXAMPLE XIV 1-Cyclopentyl-3-(4-trifluoromethylphenyl)-propane- 1,3-dione 1.97 kg of potassium tert-butoxide, 2.26 kg of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong>, 1.66 kg of p-trifluoromethylacetophenone and 36 g of 18-crown-6 ether were refluxed in 18 liters of tetrahydrofuran for 4 hours. Quenching of the reaction was carried out using 16 liters of 10percent strength hydrochloric acid at room temperature. The aqueous phase was extracted with ethyl acetate and the combined organic phases were washed with saturated sodium chloride solution. After distilling off the solvent, the residue was distilled in an oil-pump vacuum at 1.5 mbar. 1.664 kg of 1-cyclopentyl-3-(4-trifluoromethylphenyl)propane-1,3-dione resulted as an oil, which crystallized completely on allowing to stand. Boiling point: 138-145° C./1.5 mbar.

Reference： [1]Patent: US6069148,2000,A
[2]Patent: US6207671,2001,B1

26
[ 4630-80-2 ]
[ 107-30-2 ]
[ 220875-97-8 ]

Yield	Reaction Conditions	Operation in experiment
100%		Methyl 1-(methoxymethyl)cyclopentanecarboxylateButyl-lithium (25 ml_ of a 1.6 M solution in hexanes, 40.1 mmol) was slowly added to a solution of diisopropylamine (4.1 g, 40.1 mmol) in anhydrous THF (48 ml_), cooled at -78 0C by means of an acetone-CO2 bath under an argon atmosphere, and the solution stirred at -78 0C for 30 min. Then, a solution of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (5.0 g, 39.0 mmol) in THF (25 ml_) was slowly added at - 78 0C and the mixture allowed to warm to -40 0C and stirred at that temperature for 30 min. Then, a solution of chloromethyl methyl ether (3.26 g, 39.0 mmol) in THF (12.5 ml_) was slowly added and the mixture allowed to reach room temperature and stirred overnight. THF was evaporated and the residue diluted with water and ethyl acetate. Phases were separated and the aqueous phase was extracted again with ethyl acetate. The combined organic phases were dried over Na2SO4 and concentrated to dryness, thus obtaining 6.8 g of the title compound with quantitative yield as a crude product that was used as such in the following step. 1H RMN (300 MHz, CDCI3) delta: 1.55-1.75 (m, 6H), 2-2.15 (m, 2H), 3.33 (s, 3H), 3.45 (s, 2H), 3.72 (s, 3H).

Reference： [1]Patent: WO2009/77608,2009,A1 .Location in patent: Page/Page column 111

27
[ 1143514-07-1 ]
[ 4630-80-2 ]
[ 1143514-25-3 ]

Reference： [1]Organic Letters,2009,vol. 11,p. 1861 - 1864

28
[ 4630-80-2 ]
[ 3430-22-6 ]
[ 1190962-59-4 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium hexamethyldisilazane; In tetrahydrofuran; at -78 - 20℃; for 2.25h;Inert atmosphere;	EXAMPLE 61 120N-(5-(l-piperazinyl)-2-pyridinyl)spiro[cyclopentane-l,9'- pyrido [4',3' :3,4] cyclopenta[l,2-d] pyrimidin]-2'-amine 1212-(3-Bromo-4-pyridinyl)-l-cyclopentylethanone (121) Under a nitrogen atmosphere LiHMDS (LOM solution in tetrahydrofuran, 49.6 ml, 49.6 mmol) was added to a solution of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (3.630 g, 28.3 mmol) and 3-bromo-4-methylpyridine (2.62 ml, 23.6 mmol) in 10ml of anhydrous THF over a period of 5min at -780C. AfterlOmin the solution was allowed to warm to 2O0C and stirred for 2hours. The solution was then cooled in ice water, before the pH was adjusted to 4.5 with 25percent citric acid. After extraction with DCM the organic layer was dried over Na2SO4 and then concentrated to afford 2-(3-bromo-4-pyridinyl)-l-cyclopentylethanone (121) (6.86g, crude). 1H NMR (500 MHz, DMSO-d6) delta 8.68 (IH, s), 8.48 (IH, d, J = 4.9Hz), 7.37 (H, d, J = 4.9 Hz), 4.07 (2H, s), 3.08 (IH, ddd, Jl = 16.1 Hz, J2 = 7.3 Hz, J3 = 1.2 Hz), 1.80- 1.85 (2H, m), 1.72-1.77 (2H, m), 1.55-1.59 (4H, m); LCMS-ESI (POS), M/Z, M+l : Found 268.0

Reference： [1]Patent: WO2009/126584,2009,A1 .Location in patent: Page/Page column 105

29
[ 4630-80-2 ]
[ 1069-72-3 ]
[ 623146-85-0 ]

Yield	Reaction Conditions	Operation in experiment
79%		To <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (1 g) in THF (8 ml) at-61 °C is added a solution of 2M LDA (9.8 ml). The mixture is stirred at room temperature for 15 minutes, then 2-bromo-N, N-diethylethanarnine hydrobromide (2.04 g) is added at-61 °C. The mixture is stirred for 5 minutes at this temperature, then at room temperature. The solution became yellow and was diluted with water (30 ml). The organic phase is extracted twice with a brine solution (30 ml). The pH of the organic phase is ajusted to 4 with 6N HC1. After decantation, the aqueous phase is extracted with CH2C12 (20 ml) and the pH of aqueous phase ajusted to 12 with 6 N NaOH. After decantation, the organic phase is dried over MgSO4 and concentrated. The residue is treated with diethyl ether (10 ml) and the white solid is filtrated. Methyl 1-[2-(diethylamino) ethyl] cyclopentanecarboxylate 280 is obtained as a yellow liquid after concentration of the ether solution. Yield: 79 percent. MS (MH+) : 228.

Reference： [1]Patent: WO2003/93237,2003,A1 .Location in patent: Page/Page column 72

30
[ 3587-60-8 ]
[ 4630-80-2 ]
[ 1228343-63-2 ]

Yield	Reaction Conditions	Operation in experiment
		prparation of intermediate 6A:l-((benzyloxy)methyl)cyclopentanecarboxylic acid methyl esterCyclopentanecarboxylic acid methyl ester (1.28 g, 10 mmol) was dissolved in 20 mL of tetrahydrofuran, to which was added dropwise a tetrahydrofuran solution of KHMDS (3.0 g, 15 mmol) at -78 °C under nitrogen protection. After the addition was completed, the reaction proceeded at -78 °C for further 30 min, after which benzyl chloromethyl ether (2.03 g, 13 mmol) was added. The reaction solution was allowed to warm up to room temperature and reacted overnight. Water was added and the reaction solution was extracted with ethyl acetate. The organic phase was combined, dried, filtered, and rotary evaporated to give 1.69 g of colorless liquid 6A. Yield: 68.1percent. The crude product was used directly in the next step without further purification.MS (ESI, m/z): [M+H]+: 249.1.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 2617 - 2621
[2]Patent: WO2013/56679,2013,A1 .Location in patent: Page/Page column 41-42

31
[ 4630-80-2 ]
[ 1228894-34-5 ]

Reference： [1]Organic Letters,2010,vol. 12,p. 2810 - 2813

32
[ 4630-80-2 ]
[ 32811-75-9 ]

Reference： [1]Science,2010,vol. 327,p. 533 - 571

33
[ 513-38-2 ]
[ 4630-80-2 ]
C₁₁H₂₀O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		The alpha-isobutylcyclopentanecarboxylic acid used as a starting material for the products in Examples 42-44 below was generated by alkylation of the methyl ester of cyclopentanecarboxylic acid (Ig, 7.8 mmol) using LDA (2M, 8.9 mL, 2.2 eq) and isobutyl iodide (excess) in THF (25 mL) at -78° C to RT with stirring overnight. Extractive workup (2 x 50 mL EtOAc) after quenching with water, followed by washing with brine, drying over sodium sulfate, and concentration under reduced pressure gave the crude alkylated ester. Hydrolysis of this material with 6M NaOH (1 mL) in MeOH: THF (5 mL: 5 mL) in a pressurized vessel at 100° C using microwave radiation for 45 min; concentration of the reaction to dryness, acidification, and purification using silica gel chromatography (eluent: 10: 1 hexanes: EtOAc -> 2: 1 hexanes: EtOAc) gave the desired alpha- isobutylcyclopentanecarboxylic acid (650 mg), which could be converted into the thiazole products of Examples 43-35 via the corresponding ketone and bromoketone intermediates and coupling with thiourea derivatives, and other procedures as similarly exemplified in Example 41.

Reference： [1]Patent: WO2010/25142,2010,A1 .Location in patent: Page/Page column 60

34
[ 4630-80-2 ]
[ 5031-78-7 ]
[ 1266160-72-8 ]

Yield	Reaction Conditions	Operation in experiment
63%	With sodium hydride; In tetrahydrofuran; ethanol; mineral oil; for 5.5h;Reflux;	Example 1; 6-Cyclopentyl-4-(4-phenoxyphenyl)-1H~pyrazolo[3,4-b]pyridin-3-amineStep 1:[00140] Sodium hydride (1.508 g, 37.7 mmol, 60percent suspension in mineral oil) was added in small portions to a solution of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (1.449 g, 11.31 mmol) and 1 -(4-phenoxyphenyI)ethanone (2,00 g, 9.42 mmol) in THF (100 mL). Ethanol (0.5 mL) was then added. The mixture was heated to reflux for 5.5 h, quenched with saturated NaCI (50 mL) and acidified to pH 2 with 1 N HCI. THF was evaporated in vacuo. The residue was extracted with ethyl acetate (3x50 mL). The combined extracts were washed with brine (10 mL), dried (MgSO4) and concentrated. Silica gel chromatography, loading with 5percent ethyl acetate in hexanes and eluting with 5-20percent ethyl acetate in hexanes, gave l-cyclopentyl-3-(4-phenoxyphenyl)propane-1,3-dione as white solid (1.837 g, 63percent yield). MS (ES+) m/z: 309 (M+H); LC retention time: 5.015 min (analytical HPLC Method A).

Reference： [1]Patent: WO2011/19780,2011,A1 .Location in patent: Page/Page column 54

35
[ 4630-80-2 ]
[ 100-06-1 ]
[ 1266160-78-4 ]

Yield	Reaction Conditions	Operation in experiment
56%	With sodium hydride; In tetrahydrofuran; mineral oil; for 11h;Reflux;	Example 2; 4-(4-(Benzyloxy)phenyl)-6-cyclopentyl-1H-pyrazolo[3s4-b]pyridin-3-amine Step 1:[00144] Sodium hydride (1.378 g, 59.9 mmol, 60percent suspension in mineral oil) and ethanol (2.0 mL) were added to a solution of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (6.14 g, 47.9 mmol) and l-(4-metfaoxyphenyl)ethanone (6,00 g, 40.0 mmol) in THF (200 mL). The mixture was heated to reflux for 11 h, quenched with water (100 mL) and acidified to pH~2 with 1 N HCl. The THF solvent was evaporated in vacuo. The residue was extracted with ethyl acetate (3x100 mL). The combined extracts were washed with brine (25 mL), dried (MgSO4) and concentrated. Silica gel chromatography, loading with hexanes and small amount of toluene and eluting with 0-15percent ethyl acetate in hexanes, gave i-cyclopentyl-3-(4-methoxyphenyl)propane~1,3-dione as yellow liquid (5.494 g, 56percent yield). MS (ES+) m/z: 247 (M+H); LC retention time: 4.510 and 3.578 min, likely a mixture of keto and enol forms (analytical HPLC Method A).

Reference： [1]Patent: WO2011/19780,2011,A1 .Location in patent: Page/Page column 56-57

36
[ 4630-80-2 ]
[ 1276125-36-0 ]
[ 1276126-05-6 ]

Yield	Reaction Conditions	Operation in experiment
63%		Step 1:To a solution of diisopropyl amine (4.23 g, 29.7 mmol) in THF (40 mL) at -78 C. was added n-BuLi (1.6 M in hexane, 17.1 mL, 27 mmol). The dry ice-acetone bath was removed after the addition. The reaction mixture was stirred for 10 min and then cooled to -78 C. A solution of cyclopentanecarboxylic acid methyl ester (3.4 g, 27 mmol) in THF (15 mL) was added to the above prepared LDA solution dropwise at -78 C. and stirred at -78 C. for 15 minutes. Then a solution of compound 3-1 (3.18 g, 9 mmol) and HMPA (1.62 mL, 9 mmol) in THF (35 mL) was added dropwise. After the mixture was stirred at -78 C. for 30 minutes, the reaction mixture was poured into saturated aqueous NH4Cl solution (250 mL). The organic layer was separated and the aqueous layer was extracted with DCM (100 mL×3). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate=50:1) to give compound 19-1 (2 g, 63%) as a yellow oil. 1H NMR (300 MHz, CDCl3) delta 7.43 (t, 1H, J=7.7 Hz), 7.30-7.26 (m, 1H), 7.07 (d, 1H, J=7.5 Hz), 3.65 (s, 3H), 2.76-2.68 (m, 2H), 2.15-2.02 (m, 2H), 1.72-1.59 (m, 7H), 1.49-1.40 (m, 2H), 1.36-1.17 (m, 5H). LC-MS: 354, 356 [M+1]+, tR=3.190 min.

Reference： [1]Patent: US2011/71179,2011,A1 .Location in patent: Page/Page column 37; 38

37
[ 115827-95-7 ]
[ 4630-80-2 ]
[ 1360569-15-8 ]

Yield	Reaction Conditions	Operation in experiment
		Step 2: Synthesis of methyl l-(ethoxymethyl)cyclopentanecarboxylate:To a solution of diisopropylamine (44.4 ml, 0.3169 mol) in tetrahydrafuran (200 ml), n-BuLi (2.5M, 105.6 ml, 0.264 mol) was added in hexane at 0°C and the reaction mixture was allowed to stir at same temperature for about 10-15 minutes. The reaction mixture was stirred at room temperature for about 45 minutes. <strong>[4630-80-2]Methyl cyclopentanecarboxylate</strong> (step 1, 15 g, 0.15067 mol) in tetrahydrafuran (150 ml) was added drop-wise at -78°C to reaction mixture. The reaction mixture was stirred at same temperature for about 2 hours and then (iodomethoxy)ethane (12.67 ml, 0.1584 mol) was added drop- wise. The reaction was maintained at -78°C for an hour and allowed to attain room temperature. Reaction rnixture was stirred overnight at room temperature and quenched at 0°C with saturated NH4C1 solution. Tetrahydrafuran was concentrated over vaccum and the compound was extracted with ethyl acetate. The organic layer was washed with saturated brine solution, dried over anhydrous Na2S04 and concentrated. The obtained crude product was directly used for the next step. Crude yield: 10 gm. 1H NMR (CDC13, 300 MHz): delta 4.11 (q, 2H, J = 7.2 Hz); 2.13-1.41 (m, 13H); 1.21 (t, 3H, J = 7.2 Hz); 0.81 (t, 3H, J = 7.5 Hz). ESI Mass: 187 (M+l)

Reference： [1]Patent: WO2012/25857,2012,A1 .Location in patent: Page/Page column 67-68

38
[ 4630-80-2 ]
[ 441774-57-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 1 h / -78 °C 1.2: 1 h / -78 - 20 °C 2.1: lithium aluminium tetrahydride / diethyl ether / 2 h / 0 °C
	Multi-step reaction with 2 steps 1.1: n-butyllithium; isopropylamine / tetrahydrofuran; hexane / 0.2 h / -78 °C 1.2: 16 h / -78 - 20 °C 2.1: lithium aluminium tetrahydride / diethyl ether / 1 h / 0 °C

Reference： [1]Kubota, Koji; Yamamoto, Eiji; Ito, Hajime [Journal of the American Chemical Society, 2013, vol. 135, # 7, p. 2635 - 2640]
[2]Escudero, Julien; Bellosta, Véronique; Cossy, Janine [Angewandte Chemie - International Edition, 2018, vol. 57, # 2, p. 574 - 578][Angew. Chem., 2018, vol. 130, p. 583 - 587,5]

39
[ 4630-80-2 ]
[ 106-95-6 ]
[ 153579-96-5 ]

Yield	Reaction Conditions	Operation in experiment
		To an oven-dried round bottom flask was added a solution of freshly distilleddiisopropylamine (1.6 mL, 11.3 mmol) in dry THF (10 mL), together with n-BuLisolution (1.5 M, 5.7 mL, 8.58 mmol) at 0 C. After 30 min, the resulting mixture wascooled to -78 C and ester 2.8e (1.00 g, 7.80 mmol) was added. After 30 min, allylbromide (0.75 mL, 8.58 mmol) was added to the mixture and it was stirred for 10 min.The mixture was warmed to room temperature. After 22 h, the solution was quenchedwith water (20 mL) and extracted with Et2O (20 mL × 3). The combined organic layerswere washed with brine, dried over anhydrous MgSO4, filtered and concentrated in vacuoto afford crude ester 2.9e.

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 574 - 578
Angew. Chem.,2018,vol. 130,p. 583 - 587,5
[2]Journal of the American Chemical Society,2013,vol. 135,p. 2635 - 2640
[3]Synlett,2017,vol. 28,p. 1570 - 1575

40
[ 4630-80-2 ]
[ 95-92-1 ]
methyl 1-[ethoxy(oxo)acetyl]cyclopentanecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
12.28 g	With lithium diisopropyl amide; In tetrahydrofuran; n-heptane; ethylbenzene; at -78℃; for 1h;	At -78° C., 10.00 g (78.020 mmol) of <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> and 13.683 g (93.624 mmol) of ethyl oxalate were initially charged in 200 ml of tetrahydrofuran, 46.812 ml (93.624 mmol) of lithium diisopropylamide (2M in tetrahydrofuran/heptane/ethylbenzene) were added and the mixture was then stirred at -78° C. for 1 h. The cooling bath was then removed, and the mixture was stirred at room temperature for 1 h. The mixture was then cooled to 0° C., and 1M hydrochloric acid was added. The mixture was then extracted three times with ethyl acetate and the organic phases were combined. The organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulphate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate gradient). This gave 12.28 g (68percent of theory) of the title compound. MS (Method 6): MS: m/z=229 (M+H)+

Reference： [1]Patent: US2014/357637,2014,A1 .Location in patent: Paragraph 1073 - 1075

41
[ 1942-45-6 ]
[ 4630-80-2 ]
2,5-dicyclopentyl-3,4-dipropylfuran [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With bis(cyclopentadienyl)titanium dichloride; ethylaluminum dichloride; magnesium; In tetrahydrofuran; at 0 - 60℃; for 6h;Inert atmosphere;	General procedure: A 50-mL glass reactor was charged under dry argon at 0 °C with 15 mL of THF, and 20 mmol of magnesium powder, 20 mmol of EtAlCl2, and 1.0 mmol of Cp2TiCl2 were added in succession under stirring. After 1 h, 10 mmol of symmetrical acetylene and 20 mmol of ester were added, and the mixture was heated to 60 °C and stirred for 6 h at that temperature. When the reaction was complete, the mixture was cooled to 0 °C in a stream of argon, 10?15 mL of diethyl ether was added, and the mixture was hydrolyzed with 5 percent aqueous HCl. The organic layer was separated, the aqueous layer was extracted with two portions of diethyl ether, and the combined extracts were washed with a solution of NaHCO3 until neutral washings and dried over MgSO4. The product was isolated by vacuum distillation.

Reference： [1]Russian Journal of Organic Chemistry,2015,vol. 51,p. 1277 - 1281
Zh. Org. Khim.,2015,vol. 51,p. 1303 - 1307,5

42
(S<SUB>S</SUB>)-2-methyl-N-(2,2,2-trifluoroethylidene)-propane-2-sulfinamide [ No CAS ]
[ 4630-80-2 ]
methyl 1-((S)-2,2,2-trifluoro-1-((S)-2-methylpropan-2-ylsulfinamido)ethyl)cyclopentanecarboxylate [ No CAS ]
methyl 1-((R)-2,2,2-trifluoro-1-((S)-2-methylpropan-2-ylsulfinamido)ethyl)cyclopentanecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: Into an oven-dried reaction vial flushed with N2 were taken esters 8 (0.60 mmol) and anhydrous toluene (3.0 mL). The reaction vial was cooled to ?78°C and LDA (2M in THF, 0.36 mL) was added dropwise with stirring. After 1h at ?78°C, sulfinylimine 7 (0.5 mmol) dissolved in anhydrous toluene (2.0 mL) was added dropwise. Stirring was continued for 2 h with the temperature gradual rising to room temperature, then the reaction was quenched with saturated H2O (3.0 mL). The organic layer was taken and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layers were dried with anhydrous Na2SO4, filtered and the solvent was removed to give the crude product 9, which was purified by column chromatography (hexane/EtOAc, 4:1).

Reference： [1]Tetrahedron,2015,vol. 71,p. 9550 - 9556

43
[ 17004-42-1 ]
[ 4630-80-2 ]
1-(carbomethoxy)-1-(4-methoxybenzylthio)cyclopentane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%		A 2.5 M solution of BuLi in hexane (2.77 mmol; 1.1 ml; 1.2 eq) is added at ?10° C. to a solution of DIPA (diisopropylethylamine) (3 mmol; 1.3 eq; 420 mul) in THF (9 ml) under inert atmosphere. The mixture is stirred for 1 hour at 0° C. This LDA solution, freshly prepared, is added dropwise to a solution of cyclopentanoic acid methyl ester in 5 ml of THF at ?55° C. The mixture is stirred for 1 hour at ?55° C. under inert atmosphere. HMPA (hexylmethylphophoramide) (3.46 mmol; 1.5 eq; 610 mul) is added and the mixture is stirred for 10 minutes at the same temperature. A solution of 4-methoxybenzyl mercaptan disulfide (3 mmol; 1.3 eq; 920 mg) in 12 ml of THF is then added dropwise at ?55° C. After returning to room temperature, the mixture is stirred overnight. The mixture is partitioned between 10 ml of saturated NH4Cl and 20 ml of AcOEt. The organic phase is washed with saturated NH4Cl (2×10 ml), saturated NaCl (2×15 ml), dried on Na2SO4 and then concentrated under reduced pressure to yield the crude product which is purified by chromatography on silica gel. (0262) C(R2R3)=Cyclopentyl: oil (Yield: 40percent) (0263) HPLC: Atlantis T3, CH3CN (0.1percent TFA)/H2O (0.1percent TFA) Gradient 30-90percent 10 min, Rt=9.68 min (0264) NMR (CDCl3, 200 MHz): 1.60-2.40 (8H, m); 3.67 (3H, s); 3.77 (2H, s); 3.80 (3H, s); 6.83 (2H, d); 7.24 (2H, d)

Reference： [1]Patent: US2015/299116,2015,A1 .Location in patent: Paragraph 0260-0264

44
[ 1000045-33-9 ]
[ 4630-80-2 ]
methyl 1-(4-chloro-3-(3-methoxypropoxy)benzyl)cyclopentane carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%		To LDA (17.03 ml, 17.03 mmol) (1M in THF) at 0 oc was added<strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (1.75 g, 13.6 mmol) and the mixture stirred for 5 min. Asolution of 4-(bromomethyl)-1-chloro-2-(3-methoxypropoxy)benzene (2 g, 6.8 mmol) in THF(5ml) was added dropwise then the mixture was allow to warm toRT. The mixture wasquenched with ice and NH4CI (aq), and then extracted with EtOAc. The organics werecombined, dried (brine, Na2S04), and concentrated to an oil. The oil was purified on silicagel hex:EtOAc (eluting at -1 0percent) to give methyl 1-(4-chloro-3-(3- methoxypropoxy)benzyl)cyclopentane-1-carboxylate (2.28 g, 6.69 mmol, 98percent yield) as ayellow oil. LCMS (ESI) (m/z): 363.3 (M+23t.

Reference： [1]Patent: WO2018/154466,2018,A1 .Location in patent: Paragraph 001390; 001392; 001393; 001394

45
[ 4630-80-2 ]
[ 55667-12-4 ]
1-(3-(benzyloxy)-4-methoxybenzyl)cyclopentanecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%		n-Butyllithium (2.5 M in hexanes) (1.24 ml, 3.09 mmol) was addeddropwise to a -78 oc solution of diisopropylamine (0.440 ml, 3.09 mmol) in tetrahydrofuran(THF) (13 ml). The mixture was allowed to warm to room temperature and stirred for 15minutes. The mixture was cooled to -78 oc before <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> (0.355ml, 2.81 mmol) was added dropwise. The mixture was warmed to 0 oc and stirred for 30minutes before being cooled again to -78 °C. A solution of 2-(benzyloxy)-4-(bromomethyl)-1-methoxybenzene (1.035 g, 3.37 mmol) in tetrahydrofuran (THF) (5 ml) was addeddropwise. The mixture was stirred an additional 15 minutes at -78 oc and then allowed towarm to room temperature and stirred overnight. The mixture was diluted with ethylacetate, washed with saturated ammonium chloride, washed with brine, and concentrated.The residue was purified by medium pressure reverse phase chromatography (C18 Iacetonitrile I water I 0.1percent formic acid I 10percent to 100percent gradient). Fractions wereconcentrated. The residue was dissolved in acetonitrile and the mixture concentrated in order to azeotrope remaining water. Drying under vacuum gave methyl 1-(3-(benzyloxy)-4-methoxybenzyl)cyclopentane-1-carboxylate (716 mg, 2.02 mmol, 72 percent yield) as a clear oil.LCMS (ESI) mlz: 377.3 (M+Nat.

Reference： [1]Patent: WO2018/154466,2018,A1 .Location in patent: Paragraph 001522; 001524; 001525

46
[ 4630-80-2 ]
[ 27104-73-0 ]
C₁₈H₁₉NO₄ [ No CAS ]
C₁₈H₁₉NO₄ [ No CAS ]

Reference： [1]ACS Catalysis,2018,vol. 8,p. 11847 - 11853

47
[ 111-24-0 ]
[ 4630-80-2 ]
methyl 1-(5-bromopentyl)cyclopentanecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With lithium diisopropyl amide; In tetrahydrofuran; at 0 - 20℃;Inert atmosphere;	Under the argon gas protection, 6 <strong>[4630-80-2]methyl cyclopentanecarboxylate</strong> 1.28 g (10 mmol) and 7 1,5-dibromopentane 2.49 g (11 mmol) were added to the reaction flask, dissolved in 50 mL of 8 tetrahydrofuran, and cooled to 0° C. 9 LDA (0.467 mmol) was slowly added in a drop wise manner for about 1 hour. After then, the reaction was stirred overnight at room temperature, and monitored by TLC on the next day. The reaction was quenched by the addition of a saturated aqueous solution of 10 ammonium chloride. After the addition, the mixture was extracted three times with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, concentrated and purified by using column chromatography with PE:EA (v/v)=100:1, to provide 1.7 g of compound B3 as a pale yellow liquid, yield 62percent. 1H NMR (300 MHz, CDCl3) delta3.63 (s, 3H), 3.36 (t, 2H), 2.05-2.09 (m, 2H), 1.78-1.83 (m, 2H), 1.54-1.60 (m, 6H), 1.35-1.44 (m, 4H), 1.18-1.21 ppm (m, 2H).

Reference： [1]Patent: US2019/39989,2019,A1 .Location in patent: Paragraph 0082-0084

48
[ 4630-80-2 ]
[ 73183-34-3 ]
2,2'-(cyclopentylmethylene)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With ethanol; iron(II) bromide; sodium t-butanolate; In toluene; at 100℃; for 24.0833h;Inert atmosphere; Glovebox;	General procedure: In the glove box, a conjugated boronic acid pinacol borate (1.2 mmol, 304.8 mg) was added to a Schlick reaction tube.Ferrous (0.03mmol), sodium tert-butoxide (0.9mmol), removed from the glove box, and added ethyl hexanoate under nitrogen atmosphere(0.3 mmol, 43.3 mg), ethanol (0.3 mmol), then 2 ml of toluene was added, and after stirring for 5 minutes, the reaction tube was placed at 100 ° C.The reaction in the pot was carried out for 24 hours. After the reaction is completed, ethyl acetate extraction is added to the system, and the product is obtained by column chromatography, and the yield is73percent.

Reference： [1]Patent: CN109734737,2019,A .Location in patent: Paragraph 0040; 0041; 0042; 0044; 0045; 0046

49
[ 4630-80-2 ]
[ 1781-81-3 ]

Reference： [1]Organic Letters,2020,vol. 22,p. 3846 - 3849

50
[ 4630-80-2 ]
[ 1092939-17-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / -3 - 24 °C / Inert atmosphere 2: 4-methyl-morpholine / toluene / 0 - 5 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate / 13 h 4: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W₀₂₂-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 5: trifluoroacetic acid; phosphoric acid
	Multi-step reaction with 5 steps 1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / -14.6 - 24 °C / Inert atmosphere 2: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 4: hydrogen; Walphos SL-W₀₂₂-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 5: trifluoroacetic acid; phosphoric acid
	Multi-step reaction with 5 steps 1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / -14.6 - 24 °C / Inert atmosphere 2: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 4: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W₀₂₂-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 5: trifluoroacetic acid; phosphoric acid

	Multi-step reaction with 6 steps 1.1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / -14.6 - 24 °C / Inert atmosphere 2.1: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 3.1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 23 °C 4.1: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W₀₂₂-1 / dichloromethane / 17 h / 23 °C / 7500.75 Torr / Sealed tube 5.1: trifluoroacetic acid / toluene / 0.25 h / 100 °C 5.2: 0.25 h / 40 °C 6.1: isopropanol
	Multi-step reaction with 6 steps 1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / -14.6 - 24 °C / Inert atmosphere 2: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 4: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 5: phosphoric acid / isopropanol; dichloromethane / 20 °C 6: isopropanol
	Multi-step reaction with 6 steps 1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / -14.6 - 24 °C / Inert atmosphere 2: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 4: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W₀₂₂-1 / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 5: phosphoric acid / isopropanol; dichloromethane / 20 °C 6: isopropanol
	Multi-step reaction with 6 steps 1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / -14.6 - 24 °C / Inert atmosphere 2: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 4: hydrogen; Walphos SL-W₀₂₂-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 5: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 6: isopropanol
	Multi-step reaction with 6 steps 1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / -14.6 - 24 °C / Inert atmosphere 2: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 4: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W₀₂₂-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 5: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 6: isopropanol

Reference： [1]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[2]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[3]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[4]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[5]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[6]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[7]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[8]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1

51
[ 4630-80-2 ]
[ 3400-45-1 ]

Yield	Reaction Conditions	Operation in experiment
99%	With pyrographite; sodium hydroxide In water at 20℃; for 24h;	General procedure for the alkaline hydrolysis of ester 1 mediated by activated charcoal General procedure: A solution of NaOH (120 mg, 3.0 mmol) in water (2.0 mL) was added to a mixture of ester 1g (284 mg, 2.0 mmol) and activated charcoal (400 mg) in a 10 mL flask. The mixture was stirred at 700 rpm at room temperature for 3 minutes. After stirring the mixture at 400 rpm for 24 h, the mixture was acidified with 3 M-sulfuric acid and Et2O (10 mL) was added. Activated charcoal was removed by filtration and washed with ether. The mixture was extracted with ether three times. The combined extracts were washed with water (2 mL×2), dried, and evaporated. The residue was purified by column chromatography on silica gel using heptane-acetone (3 : 1) as eluent to give 2g (233 mg, 91%). When the products 2 were solids, the next work-up procedure without organic solvents is possible; A solution of NaOH (120 mg, 3.0 mmol) in water (2.0 mL) was added to a mixture of ester 1b (272 mg, 2.0 mmol) and activated charcoal (400 mg) in a 10 mL flask. The mixture was stirred at 700 rpm at room temperature for 2 minutes. After stirring at 400 rpm for 24 h, activated charcoal was removed by filtration and washed with water. The filtrate was acidified with 6 M-Hydrochloric acid. The resulting precipitate was filtered and washed with water (2 mL×2) to give 2b (180 mg, 74%). Compound 2b was recrystallized from heptane.

Reference： [1]Rohand, Taoufik; Tanemura, Kiyoshi [Tetrahedron Letters, 2020, vol. 61, # 44]

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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. 4630-80-2 ] {[proInfo.proName]}

Quality Control of [ 4630-80-2 ]

Related Doc. of [ 4630-80-2 ]

Product Details of [ 4630-80-2 ]

Calculated chemistry of [ 4630-80-2 ]

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Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

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Application In Synthesis of [ 4630-80-2 ]

[ 4630-80-2 ] Synthesis Path-Upstream 1~20

[ 4630-80-2 ] Synthesis Path-Downstream 1~51

Related Functional Groups of [ 4630-80-2 ]

Aliphatic Cyclic Hydrocarbons

Esters

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[ 4630-80-2 ]