Diisopropylethylamine → 1-(s)-(1-(r)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy)-2-(r)-(4-fluorophenyl)-3-(r)-(((2-benzyloxycarbonylethyl)methylamino)-methyl)cyclopentane

HRID 1017766Notes

Reaction equation

HRID 1017766 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](C=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:40][C:41](=[O:46])[CH2:42][CH2:43][NH:44][CH3:45])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[CH3:47]CN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[F:11][C:9]([F:10])([F:12])[C:7]1[CH:6]=[C:5]([C@H:13]([O:15][C@H:16]2[CH2:20][CH2:19][C@@H:18]([CH2:45][N:44]([CH2:43][CH2:42][C:41]([O:40][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[O:46])[CH3:47])[C@@H:17]2[C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)[CH3:14])[CH:4]=[C:3]([C:2]([F:30])([F:1])[F:31])[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 69355610Benzyl 3-(methylamino)propanoate hydrochloride

Product 1

HCID 228974251-(s)-(1-(r)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy)-2-(r)-(4-fluorophenyl)-3-(r)-(((2-benzyloxycarbonylethyl)methylamino)-methyl)cyclopentane

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 500 mg of aldehyde from Step A in 5 mL of 1,2-dichloroethane was added 320 mg of N-methyl-β-alanine benzyl ester hydrochloride and 0.24 mL of DIPEA. After stirring at room temperature for 10 minutes, 470 mg of sodium triacetoxyborohydride was added. The reaction was stirred for 16 hr. The reaction was quenched with sat'd sodium bicarbonate and was extracted twice with methylene chloride. The organic layers were washed with brine, dried over sodium sulfate, combined and evaporated. The residue was purified by FC (20-30% ethyl acetate/hexanes) to give 564 mg of title compound.

Workup

  1. stirringThe reaction was stirred for 16 hr
  2. customThe reaction was quenched with sat'd sodium bicarbonate
  3. extractionwas extracted twice with methylene chloride
  4. washThe organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe residue was purified by FC (20-30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-34798065ea354a72a035eb287aa21636
Source dataset
uspto-grants-2002_11
Patent number
US06479518B2

Reaction notes

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