HCID 90014160, compound → HCID 90013939, compound

HRID 1520789Notes

Reaction equation

HRID 1520789 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19](=O)[CH2:20][C:21]([C:30]3[CH:35]=[C:34]([Cl:36])[CH:33]=[C:32]([Cl:37])[CH:31]=3)([CH2:26][N+:27]([O-])=O)[C:22]([F:25])([F:24])[F:23])=[CH:15][CH:14]=2)([F:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)C.[Ni]>[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH2:20][C:21]([C:30]4[CH:35]=[C:34]([Cl:36])[CH:33]=[C:32]([Cl:37])[CH:31]=4)([C:22]([F:25])([F:24])[F:23])[CH2:26][N:27]=3)=[CH:15][CH:14]=2)([F:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 1

HCID 90014160HCID 90014160, compound

Product 1

HCID 90013939HCID 90013939, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 702EthanolSolvent

Procedure

The solution of 3-{4-[3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-3-nitromethyl-butyryl]-phenyl}-3-fluoro-azetidine-1-carboxylic acid tert-butyl ester (1.09 g, 1.881 mmol, 1 eq.) in ethanol (12 mL) was purged with nitrogen gas for 30 minutes. To this reaction mixture was added Raney-Nickel (50% suspension in water, 0.24 g). Resulting reaction mixture was stirred under hydrogen balloon atmosphere for 16 hours at room temperature. After complete consumption of starting material, the reaction mixture was filtered through celite bed and washed with 10% MeOH in DCM (30 mL). Filtrate was concentrated to get off white solid (1.06 g, crude). Crude compound was purified by column chromatography on silica gel using 230-400 mesh. Desired compound was eluted in 7.5% ethyl acetate in n-hexane to give product as off white solid (0.27 g, 27%). 1H NMR (400 MHz, CDCl3) δ: 1.47 (s, 9H), 3.45 (d, J=17.4 Hz, 1H), 3.79 (d, J=18.84 Hz, 1H), 4.20-4.27 (m, 2H), 4.38-4.46 (m, 3H), 4.89 (d, J=17.08 Hz, 1H), 7.25-7.27 (m, 2H), 7.36-7.37 (m, 1H), 7.54 (d, J=8.28 Hz, 2H), 7.89 (d, J=8.16 Hz, 2H). LC-MS (m/z): 531.1 (M+H).

Workup

  1. customResulting
  2. customreaction mixture
  3. customAfter complete consumption of starting material
  4. filtrationthe reaction mixture was filtered through celite bed
  5. washwashed with 10% MeOH in DCM (30 mL)
  6. concentrationFiltrate was concentrated
  7. customto get off white solid (1.06 g, crude)
  8. customCrude compound was purified by column chromatography on silica gel using 230-400 mesh
  9. washDesired compound was eluted in 7.5% ethyl acetate in n-hexane

Sources & evidence

ORD record
ord-3e128c622f524ed5aea35b407d9933f5
Source dataset
uspto-grants-2015_07
Patent number
US09073912B2

Reaction notes

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