Diisopropylethylamine → methyl 3-(S)-(1-(RS)-(3,5-bis(trifluoromethyl)phenyl)ethylamino)-2-(R)-(4-fluorophenyl)cyclopentane-1-(R)-carboxylate

HRID 1289961Notes

Reaction equation

HRID 1289961 reaction equation
[NH2:1][C@H:2]1[CH2:6][CH2:5][C@@H:4]([C:7]([O:9][CH3:10])=[O:8])[C@@H:3]1[C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1.CCN(C(C)C)C(C)C.[F:27][C:28]([F:43])([F:42])[C:29]1[CH:30]=[C:31]([CH:39](Br)[CH3:40])[CH:32]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=1>C(#N)C.C(=O)(O)[O-].[Na+]>[F:27][C:28]([F:42])([F:43])[C:29]1[CH:30]=[C:31]([CH:39]([NH:1][C@H:2]2[CH2:6][CH2:5][C@@H:4]([C:7]([O:9][CH3:10])=[O:8])[C@@H:3]2[C:11]2[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=2)[CH3:40])[CH:32]=[C:33]([C:35]([F:36])([F:37])[F:38])[CH:34]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 129473971-(1-Bromoethyl)-3,5-bis(trifluoromethyl)benzeneHCID 22885810Methyl 3-(S)-(amino)-2-(R)-(4-fluorophenyl)cyclopentane-1-(R)-carboxylate

Product 1

HCID 22885643methyl 3-(S)-(1-(RS)-(3,5-bis(trifluoromethyl)phenyl)ethylamino)-2-(R)-(4-fluorophenyl)cyclopentane-1-(R)-carboxylateYield 37.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of 200 mg of amine from Example 62, 0.3 mL of DIPEA and 350 mg of 1-(RS)-(3,5-bis(trifluoromethyl)phenyl)ethyl bromide (prepared in Example 24) in 2 mL of acetonitrile was heated at 50° C. in a sealed vial for 40 h. The reaction was diluted with saturated sodium bicarbonate and extracted twice with methylene chloride. The organic layers were washed with a portion of brine, combined, dried over sodium sulfate and evaporated. The residue was purified by flash chromatography eluting with 10 to 15% ethyl acetate in hexanes to obtain 150 mg of title compound as a mixture of methyl isomers. Mass spec (NH3 /CI): 478 (M+1).

Workup

  1. extractionextracted twice with methylene chloride
  2. washThe organic layers were washed with a portion of brine
  3. dry with materialdried over sodium sulfate
  4. customevaporated
  5. customThe residue was purified by flash chromatography
  6. washeluting with 10 to 15% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-a14c3c1d9ecf46289abcf26c52c2169c
Source dataset
uspto-grants-1998_05
Patent number
US05750549

Reaction notes

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