Diisopropylethylamine → 1-(S)-(1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy)-2-(R)-(4-fluorophenyl)-3-(R)-(((R)-3-ethoxycarbonylpiperidin-1-yl)methyl)cyclopentane

HRID 1017775노트

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HRID 1017775 반응식
[F:1][C:2]([F:31])([F:30])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[CH2:20][CH2:19][C@@H:18]([CH:21]=O)[C@@H:17]2[C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Cl.[CH2:33]([O:35][C:36]([C@@H:38]1[CH2:43][CH2:42][CH2:41][NH:40][CH2:39]1)=[O:37])[CH3:34].CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[F:31][C:2]([F:1])([F:30])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[CH2:20][CH2:19][C@@H:18]([CH2:21][N:40]3[CH2:41][CH2:42][CH2:43][C@@H:38]([C:36]([O:35][CH2:33][CH3:34])=[O:37])[CH2:39]3)[C@@H:17]2[C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 228974301-(S)-(1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy)-2-(R)-(4-fluorophenyl)-3-(R)-(formyl)cyclopentaneHCID 44828658Ethyl (3R)-piperidine-3-carboxylate--hydrogen chloride (1/1)

생성물 1

HCID 228974321-(S)-(1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy)-2-(R)-(4-fluorophenyl)-3-(R)-(((R)-3-ethoxycarbonylpiperidin-1-yl)methyl)cyclopentane수율 81%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

실험 절차

To a solution of 9.8 g (22 mmole) of 1-(S)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-2-(R)-(4-fluorophenyl)-3-(R)-(formyl)cyclopentane from Step A in 100 mL of 1,2-dichloroethane was added 8.7 g (28 mmole) of (R)-3-ethoxycarbonylpiperidine hydrochloride and 4.9 mL (28 mmole) of DIPEA. After stirring at room temperature for 10 minutes, 9.2 g (44 mmole) of sodium triacetoxyborohydride was added. The reaction was stirred for 16 hours. The reaction was quenched with sat'd sodium bicarbonate and was extracted twice with methylene chloride. The organic layers were each washed with a portion of brine, dried over sodium sulfate, combined and evaporated. The residue was purified by prep LC (20-30% ethyl acetate/hexanes) to give 10.5 g of title compound.

후처리

  1. stirringThe reaction was stirred for 16 hours
  2. customThe reaction was quenched with sat'd sodium bicarbonate
  3. extractionwas extracted twice with methylene chloride
  4. washeach washed with a portion of brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe residue was purified by prep LC (20-30% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-c10b4b70464745d895e393bcdbef4002
출처 데이터셋
uspto-grants-2002_11
특허 번호
US06479518B2

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