Methyl iodide → 1-(SR)-(3,5-Bis(trifluoromethyl)phenyl)methoxy-2-(SR)-phenyl-3-(RS)-(N-(benzyloxycarbonyl)-N-methylamino) cyclopentane

HRID 1017760Notes

Reaction equation

HRID 1017760 reaction equation
[F:1][C:2]([F:38])([F:37])[C:3]1[CH:4]=[C:5]([CH2:13][O:14][CH:15]2[CH2:19][CH2:18][CH:17]([NH:20][C:21]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:22])[CH:16]2[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.I[CH3:40].[H-].[Na+]>CN(C=O)C>[F:1][C:2]([F:37])([F:38])[C:3]1[CH:4]=[C:5]([CH2:13][O:14][CH:15]2[CH2:19][CH2:18][CH:17]([N:20]([C:21]([O:23][CH2:24][C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)=[O:22])[CH3:40])[CH:16]2[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 750242431-(SR)-(3,5-Bis(trifluoromethyl)phenyl)methoxy-2-(SR)-phenyl-3-(RS)-(benzyloxycarbonylamino)cyclopentane

Product 1

HCID 865848721-(SR)-(3,5-Bis(trifluoromethyl)phenyl)methoxy-2-(SR)-phenyl-3-(RS)-(N-(benzyloxycarbonyl)-N-methylamino) cyclopentane

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 500 mg of benzyl carbamate prepared in Example 4, Step B and 0.12 mL of iodomethane in 5 mL of DMF was added 60 mg of 60% sodium hydride in mineral oil. After 2 hours, the reaction was quenched with 2N hydrochloric acid and water and extracted twice with ethyl acetate. 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 25% ethyl acetate in hexanes to obtain 500 mg of title compound as an oil. NMR (CDCl3): δ1.80-2.0 (m, 3H), 2.0-2.2 (m, 1H), 2.80 and 2.87 (2 br s, 3H), 3.05-3.15 (m, 1H), 3.9-4.0 (m, 1H), 4.36 and 4.40 (2 s, 1H), 4.4-4.55 (m, 1H), 4.55-4.85 (2 br m, 1H), 4.91 and 5.03 (2 br s, 2H), 7.0-7.3 (m, 10H), 7.58 (br s, 2H), 7.72 (s, 1H).

Workup

  1. customthe reaction was quenched with 2N hydrochloric acid and water
  2. extractionextracted twice with ethyl acetate
  3. washThe organic layers were washed with a portion of brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. customThe residue was purified by flash chromatography
  7. washeluting with 25% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-5fd08e3ee4684ee2bd37fcf6c077e2c7
Source dataset
uspto-grants-2002_11
Patent number
US06479518B2

Reaction notes

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