Phosgene → HCID 86682278, compound

HRID 540453Notes

Reaction equation

HRID 540453 reaction equation
F[C:2](F)(F)[C:3]1[CH:4]=[C:5]([C@H:13]([C@@H:15]2[CH2:20][CH2:19][CH2:18][C@@H:17]([C:21]3[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][C:22]=3[Br:31])[NH:16]2)[OH:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CCN(C(C)C)C(C)C.[C:43](Cl)(Cl)=[O:44]>C(Cl)Cl>[Br:31][C:22]1[CH:23]=[CH:24][C:25]([C:27]([F:28])([F:29])[F:30])=[CH:26][C:21]=1[C@H:17]1[N:16]2[C:43](=[O:44])[O:14][C@H:13]([C:5]3[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=[C:3]([CH3:2])[CH:4]=3)[C@@H:15]2[CH2:20][CH2:19][CH2:18]1

Participants

5

Reactant 3

HCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 86682277HCID 86682277, compound

Product 1

HCID 86682278HCID 86682278, compoundYield 68.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To (R)-[3,5-bis(trifluoromethyl)phenyl]{(2S,6S)-6-[2-bromo-5-(trifluoromethyl)phenyl]piperidin-2-yl}methanol (280 mg, 0.509 mmol) in DCM (5 mL) was added DIPEA (0.9 mL, 0.509 mmol) and phosgene (252 mg, 0.509 mmol). The reaction mixture was stirred at room temperature for 30 minutes before the solvent was removed and the reaction was diluted with ethyl acetate (15 mL) and aqueous KOH (15 mL). The organic was dried over sodium sulfate, filtered, and concentrated before purification by preparative TLC to yield (1R,5S,8aS)-5-[2-bromo-5-(trifluoromethyl)phenyl]-1-[3-methyl-5-(trifluoromethyl)phenyl]hexahydro[1,3]oxazolo[3,4-a]pyridin-3-one (200 mg, 0.347 mmol). MS ESI calc'd. for C22H16BrF9NO2 [M+H]+ 576.0 and 578.0. found 576.1 and 578.1.

Workup

  1. customwas removed
  2. additionthe reaction was diluted with ethyl acetate (15 mL) and aqueous KOH (15 mL)
  3. dry with materialThe organic was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated before purification by preparative TLC

Sources & evidence

ORD record
ord-da5c3ddc0cbb45caae6b38d17c2f4718
Source dataset
uspto-grants-2014_10
Patent number
US08871738B2

Reaction notes

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