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 1017775Notes

Reaction equation

HRID 1017775 reaction equation
[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

Participants

6

Reactant 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)

Product 1

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

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-c10b4b70464745d895e393bcdbef4002
Source dataset
uspto-grants-2002_11
Patent number
US06479518B2

Reaction notes

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