Sodium hydride → HCID 44545732, compound

HRID 1951145Notes

Reaction equation

HRID 1951145 reaction equation
[Cl:1][C:2]1[CH:31]=[CH:30][C:5]([C:6]([N:8]([CH:10]2[CH:14]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=3)[CH2:13][N:12]([C:22]([CH:24]3[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]3)=[O:23])[CH2:11]2)[CH3:9])=[O:7])=[CH:4][C:3]=1[C:32]([F:35])([F:34])[F:33].[H-].[Na+].I[CH2:39][C:40]#[N:41]>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:31]=[CH:30][C:5]([C:6]([N:8]([CH:10]2[CH:14]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=3)[CH2:13][N:12]([C:22]([CH:24]3[CH2:25][CH2:26][N:27]([CH2:39][C:40]#[N:41])[CH2:28][CH2:29]3)=[O:23])[CH2:11]2)[CH3:9])=[O:7])=[CH:4][C:3]=1[C:32]([F:34])([F:35])[F:33]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 69356Iodoacetonitrile2×HCID 67025745HCID 67025745, compound

Product 1

HCID 44545732HCID 44545732, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-chloro-N-[(3RS,4SR)-4-(4-chloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-N-methyl-3-trifluoromethyl-benzamide (216 mg, 0.382 mmol) in DMF (1 mL) was added sodium hydride (55% dispersion in mineral oil, 6 mg, 0.14 mmol). After stirring for 30 min at ambient temperature iodoacetonitrile (9 μl, 0.12 mmol) was added And the suspension was stirred for 18 h at this temperature. After the addition of further iodoacetonitrile (9 μl, 0.12 mmol) the resulting dark brown solution was stirred for further 5 h at ambient temperature. It was diluted with ethyl acetate (10 mL) and was washed with aqueous sodium carbonate (1 M, 10 mL) and brine (10 mL). The aqueous layers were extracted with ethyl acetate (10 mL) and the combined organic phases were dried over sodium sulfate. Purification by chromatography (SiO2, (ethyl acetate:triethylamine=95:5):methanol=100:0 to 70:30) afforded the title compound (45 mg, 88%) as a white foam. MS m/e: 567.1 [M]+.

Workup

  1. additionwas added
  2. stirringwas stirred for further 5 h at ambient temperature
  3. washwas washed with aqueous sodium carbonate (1 M, 10 mL) and brine (10 mL)
  4. extractionThe aqueous layers were extracted with ethyl acetate (10 mL)
  5. dry with materialthe combined organic phases were dried over sodium sulfate
  6. customPurification by chromatography (SiO2, (ethyl acetate:triethylamine=95:5):methanol=100:0 to 70:30)

Sources & evidence

ORD record
ord-f3b59ac3807d46cb8d1d9f3a5a5be1d5
Source dataset
uspto-grants-2013_03
Patent number
US08404679B2

Reaction notes

Loading…