Sodium hydride → HCID 68325504, compound

HRID 2403273Notes

Reaction equation

HRID 2403273 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:18]=[CH:17][C:16]([NH2:19])=[CH:15][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Br:22][C:23]1[CH:24]=[CH:25][C:26]([CH:29](OS(C(F)(F)F)(=O)=O)[C:30]([F:33])([F:32])[F:31])=[N:27][CH:28]=1>C1COCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:18]=[CH:17][C:16]([NH:19][CH:29]([C:26]3[CH:25]=[CH:24][C:23]([Br:22])=[CH:28][N:27]=3)[C:30]([F:33])([F:32])[F:31])=[CH:15][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 573650691,1-Dimethylethyl 3-(4-aminophenyl)-1-pyrrolidinecarboxylateHCID 86664596HCID 86664596, compound

Product 1

HCID 68325504HCID 68325504, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (RS)-3-(4-amino-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (50 mg, CAS 908334-28-1) in dry THF (0.1 ml) under an argon atmosphere was added sodium hydride (14 mg, 60% dispersion in mineral oil) and stirring was continued for 15 minutes. Trifluoro-methanesulfonic acid 1-(5-bromo-pyridin-2-yl)-2,2,2-trifluoro-ethyl ester (74 mg) was then added and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate and washed sequentially with water and with saturared brine. The organic phase was separated, dried over sodium sulphate, and concentrated in vacuo. The reside was purified by flash column chromatography (silical gel; gradient: heptane/EtOAc) to give (RS)-3-{4-[(RS)-1-(5-bromo-pyridin-2-yl)-2,2,2-trifluoro-ethylamino]-phenyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (34 mg, 36%) as a yellow oil. MS (ISP): 501.9 ([{81Br}M+H]+), 500.2 ([{79Br}M+H]+), 446.2 ([{81Br}M+H—C4H8]+), 444.1 ([{79Br}M+H—C4H8]+).

Workup

  1. stirringthe mixture was stirred overnight at room temperature
  2. washwashed sequentially with water and with saturared brine
  3. customThe organic phase was separated
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated in vacuo
  6. customThe reside was purified by flash column chromatography (silical gel; gradient: heptane/EtOAc)

Sources & evidence

ORD record
ord-29bc201d39294dd7a1aeac1022687cb8
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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