Oxalyl chloride → 5-Benzyl-6-(4-(4,4,4-trifluorobutoxy)phenyl)-6-(trifluoromethyl)-5-azaspiro[2.3]-hexan-4-one

HRID 1629781Notes

Reaction equation

HRID 1629781 reaction equation
[CH2:1]([NH:8][C:9]([C:28]1([C:31](O)=[O:32])[CH2:30][CH2:29]1)([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][C:24]([F:27])([F:26])[F:25])=[CH:16][CH:15]=1)[C:10]([F:13])([F:12])[F:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O>C(Cl)Cl.CN(C=O)C>[CH2:1]([N:8]1[C:9]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][C:24]([F:26])([F:27])[F:25])=[CH:16][CH:15]=2)([C:10]([F:12])([F:11])[F:13])[C:28]2([CH2:30][CH2:29]2)[C:31]1=[O:32])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 65578Oxalyl chlorideHCID 866858701-(1-(Benzylamino)-2,2,2-trifluoro-1-(4-(4,4,4-trifluorobutoxy)phenyl)ethyl)-cyclopropane carboxylic acid

Product 1

HCID 866858725-Benzyl-6-(4-(4,4,4-trifluorobutoxy)phenyl)-6-(trifluoromethyl)-5-azaspiro[2.3]-hexan-4-oneYield 77.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of Intermediate 14E (506 mg, 1.1 mmol) in CH2Cl2 (11 mL) was added oxalyl chloride (0.12 mL, 2.2 mmol) followed by several drops of DMF. The reaction was stirred at rt for 16 h. The solvent was removed in vacuo and the residue was purified by silica gel chromatography (24 g silica gel, eluted with EtOAc in hexanes) to provide Intermediate 14F (389 mg, 72%) as a yellow oil. LCMS Anal. Calc'd for C23H21F6NO2 457.41, found [M+H] 458.2.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was purified by silica gel chromatography (24 g silica gel, eluted with EtOAc in hexanes)

Sources & evidence

ORD record
ord-67f4e8a790e84124ac059b6e41aacc33
Source dataset
uspto-grants-2014_07
Patent number
US08791091B2

Reaction notes

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