Sodium Hydroxide → 1-[[2alpha-(4-Fluorophenyl)-3beta-[[(R)-alpha-methyl-3,5-bis(trifluoromethyl)benzyl]oxy]cyclopentane-1beta-yl]methyl]piperidine-3alpha-carboxylic acid

HRID 1017776노트

반응식

HRID 1017776 반응식
[F:1][C:2]([F:41])([F:40])[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:22]3[CH2:27][CH2:26][CH2:25][C@@H:24]([C:28]([O:30]CC)=[O:29])[CH2:23]3)[C@@H:17]2[C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[Na+]>CO>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]([O:15][C@H:16]2[CH2:20][CH2:19][C@@H:18]([CH2:21][N:22]3[CH2:27][CH2:26][CH2:25][C@@H:24]([C:28]([OH:30])=[O:29])[CH2:23]3)[C@@H:17]2[C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[CH3:14])[CH:4]=[C:3]([C:2]([F:41])([F:1])[F:40])[CH:8]=1

참가 물질

4

반응물 2

HCID 14798Sodium HydroxideHCID 228974321-(S)-(1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy)-2-(R)-(4-fluorophenyl)-3-(R)-(((R)-3-ethoxycarbonylpiperidin-1-yl)methyl)cyclopentane

생성물 1

HCID 115993661-[[2alpha-(4-Fluorophenyl)-3beta-[[(R)-alpha-methyl-3,5-bis(trifluoromethyl)benzyl]oxy]cyclopentane-1beta-yl]methyl]piperidine-3alpha-carboxylic acid수율 93.2%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

To a solution of 10.14 g (17.2 mmole) of 1-(S)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-2-(R)-(4-fluorophenyl)-3-(R)-(((R)-3-ethoxycarbonylpiperidin-1-yl)methyl)cyclopentane from Step B in 100 mL of methanol was added 17.2 mL (86 mmole) of 5N sodium hydroxide. The reaction was stirred at rt for 20 hours and was then most of the methanol was removed in vacuo. The residue was diluted with water and the pH was adjusted to 7 with 2N hydrochloric acid. The mixture was extracted 3 times with methylene chloride and each organic layer was washed with a portion of brine. The organic layers were dried over sodium sulfate and evaporated to afford 9.0 g of crude title compound as a white foam. NMR (CDCl3)δ: 1.37 (d, J=6 Hz, 3H), 1-8-2.0 (m, 2H), 2.0-2.7 (m, 12H), 2.7-3.1 (m, 2H), 3.2-3.4 (1H), 3.4-3.6 (m, 2H), 3.69 (m, 1H), 4.48 (q, J=6 Hz, 1H), 6.96 (m, 1H), 7.11 (m, 1H), 7.40 (s, 2H), 7.69 (s, 1H).

후처리

  1. custommost of the methanol was removed in vacuo
  2. additionThe residue was diluted with water
  3. extractionThe mixture was extracted 3 times with methylene chloride
  4. washeach organic layer was washed with a portion of brine
  5. dry with materialThe organic layers were dried over sodium sulfate
  6. customevaporated

출처 및 근거

ORD 기록
ord-4889c6ccc0b74b6d8b9d1dd33293be8a
출처 데이터셋
uspto-grants-2002_11
특허 번호
US06479518B2

반응 노트

불러오는 중…