Dimethylformamide → HCID 86761036, compound

HRID 1869745Notes

Reaction equation

HRID 1869745 reaction equation
C(Cl)(=O)C(Cl)=O.[F:7][C:8]([F:41])([F:40])[C:9]1[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][C:10]=1[CH2:11][N:12]1[CH2:17][CH2:16][C@H:15]([CH2:18][C:19]([OH:21])=O)[CH2:14][C@@H:13]1[C:22]1[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=1.CN(C=O)C.[Si]([CH:51]=[N+:52]=[N-:53])(C)(C)C>C(Cl)Cl.C1COCC1.CC#N>[F:41][C:8]([F:40])([F:7])[C:9]1[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][C:10]=1[CH2:11][N:12]1[CH2:17][CH2:16][C@H:15]([CH2:18][C:19]([CH:51]=[N+:52]=[N-:53])=[O:21])[CH2:14][C@@H:13]1[C:22]1[CH:23]=[CH:24][C:25]([C:28]([F:29])([F:30])[F:31])=[CH:26][CH:27]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 167693TrimethylsilyldiazomethaneHCID 57987405HCID 57987405, compound

Product 1

HCID 86761036HCID 86761036, compoundYield 101.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22177404Acetonitrile tetrahydrofuranSolvent

Procedure

Oxalyl chloride (65 μl, 0.77 mmol) was added to a suspension of (±)-cis-{1-[2,5-bis(trifluoromethyl)benzyl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetic acid (Example 56) (157 mg, 0.30 mmol) in DCM (10 ml). DMF (5 μl) was added and the pale yellow solution obtained was stirred at RT under N2, for 2 h. The yellow solution was concentrated in vacuo and oxalyl chloride removed by azeotroping with toluene to yield a yellow solid. This was dissolved in THF/MeCN (5 ml/5 ml) cooled to 0° C. and TMS diazomethane (0.3 ml, 2M in hexane, 0.60 mmol) was added under N2. The mixture was stirred for 5 h at 0° C. and then at RT for 16 h. The yellow solution was evaporated in vacuo to give a pale brown gum (164 mg). The crude product was purified by chromatography (silica, 10% EtOAc/isohexane) to give a clear gum (91 mg, 56%). M/Z (ES+) 488 (MH+).

Workup

  1. customthe pale yellow solution obtained
  2. concentrationThe yellow solution was concentrated in vacuo and oxalyl chloride
  3. customremoved
  4. customby azeotroping with toluene
  5. customto yield a yellow solid
  6. temperaturecooled to 0° C.
  7. stirringThe mixture was stirred for 5 h at 0° C.
  8. waitat RT for 16 h
  9. customThe yellow solution was evaporated in vacuo

Sources & evidence

ORD record
ord-4493e1a4672748c7bbf27f7d15f0ea43
Source dataset
uspto-grants-2009_12
Patent number
US07638629B2

Reaction notes

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