tert-butyl 5'-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluoro-3-(nitromethyl)butanoyl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate → tert-butyl 5'-(3-(3,5-dichloro-4-fluorophenyl)-3-(trifluoromethyl)-3,4-di hydro-2H-pyrrol-5-yl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

HRID 1508298Notes

Reaction equation

HRID 1508298 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]([CH2:37][N+:38]([O-])=O)([C:33]([F:36])([F:35])[F:34])[CH2:11][C:12]([C:14]2[CH:15]=[C:16]3[C:20](=[CH:21][CH:22]=2)[C:19]2([CH2:25][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:23]2)[O:18][CH2:17]3)=O)[CH:5]=[C:6]([Cl:9])[C:7]=1[F:8]>C(O)C>[Cl:9][C:6]1[CH:5]=[C:4]([C:10]2([C:33]([F:34])([F:36])[F:35])[CH2:11][C:12]([C:14]3[CH:15]=[C:16]4[C:20](=[CH:21][CH:22]=3)[C:19]3([CH2:23][N:24]([C:26]([O:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[O:27])[CH2:25]3)[O:18][CH2:17]4)=[N:38][CH2:37]2)[CH:3]=[C:2]([Cl:1])[C:7]=1[F:8]

Participants

3

Reactant 1

HCID 89994583tert-butyl 5'-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluoro-3-(nitromethyl)butanoyl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

Product 1

HCID 89994562tert-butyl 5'-(3-(3,5-dichloro-4-fluorophenyl)-3-(trifluoromethyl)-3,4-di hydro-2H-pyrrol-5-yl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylateYield 40.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To the solution of tert-butyl 5′-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluoro-3-(nitromethyl)butanoyl)-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate (Preparation 7, 1.2 g, 1.98mmol) in ethanol (10 mL) nitrogen was purged for 30 minutes and was added pre-washed Raney-Nickel (0.24 g, 50% suspension in water). Resulting reaction mixture was stirred under hydrogen atmosphere using balloon for 16 hours at room temperature. After complete conversion of starting material, the reaction mixture was filtered through celite bed. The bed was washed with 10% MeOH in DCM (30 mL). Combined filtrate was concentrated under vacuum to get 1.1 g of crude, off white solid. Crude compound was purified by column chromatography on silica gel (230-400 mesh). Desired compound was eluted in 7% EtOAc in n-Hexane to afford off white semi solid (451 mg, 40.63%). 1H NMR (400 MHz, CDCl3) δ: 1.47 (s, 9H), 3.44 (d, J=17.2 Hz 1H), 3.76-3.81 (m, 1H), 4.13 (d, J=9.68 Hz, 2H), 4.32 (d, J=9.68 Hz, 2H), 4.42 (d, J=17.12 Hz 1H), 4.84-4.89 (m, 1H), 5.13 (s, 2H), 7.32 (d, J=5.96 Hz, 2H), 7.54 (d, J=7.92 Hz 1H), 7.73 (s, 1H), 7.83 (d, J=7.88 Hz 1H). LC-MS (m/z): 558.8 (M+H).

Workup

  1. additionwas added
  2. washpre-washed Raney-Nickel (0.24 g, 50% suspension in water)
  3. customResulting
  4. customreaction mixture
  5. customfor 16 hours
  6. customat room temperature
  7. filtrationAfter complete conversion of starting material, the reaction mixture was filtered through celite bed
  8. washThe bed was washed with 10% MeOH in DCM (30 mL)
  9. concentrationCombined filtrate was concentrated under vacuum
  10. customto get 1.1 g of crude
  11. customCrude compound was purified by column chromatography on silica gel (230-400 mesh)
  12. washDesired compound was eluted in 7% EtOAc in n-Hexane

Sources & evidence

ORD record
ord-109b076a8c8e45b89731e73e1507bad0
Source dataset
uspto-grants-2015_12
Patent number
US09221835B2

Reaction notes

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