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 1017776Notes

Reaction equation

HRID 1017776 reaction equation
[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

Participants

4

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-4889c6ccc0b74b6d8b9d1dd33293be8a
Source dataset
uspto-grants-2002_11
Patent number
US06479518B2

Reaction notes

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