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

HRID 1508303Notes

Reaction equation

HRID 1508303 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]([CH2:36][N+:37]([O-])=O)([C:32]([F:35])([F:34])[F:33])[CH2:10][C:11]([C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[C:18]2([CH2:24][N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:22]2)[O:17][CH2:16]3)=O)[CH:5]=[C:6]([Cl:8])[CH:7]=1>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:32]([F:34])([F:33])[F:35])[CH2:10][C:11]([C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[C:18]3([CH2:24][N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:22]3)[O:17][CH2:16]4)=[N:37][CH2:36]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

3

Reactant 1

HCID 89994541tert-butyl 5'-(3-(3,5-dichlorophenyl)-4,4,4-trifluoro-3-(nitromethyl)butanoyl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

Product 1

HCID 89994543tert-butyl 5'-(3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-3,4-dihydro-2H-pyrrol-5-yl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

The solution of tert-butyl 5′-(3-(3,5-dichlorophenyl)-4,4,4-trifluoro-3-(nitromethyl)butanoyl)-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate) (Preparation 11, 1.02 g, 1.74 mmol) in ethanol (12 mL) was purged with nitrogen gas for 30 minutes. To this reaction mixture 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 completion of starting material, the reaction mixture was filtered through celite bed and bed was washed with 10% MeOH in DCM (30 mL). Filtrate was concentrated under reduced pressure to get off white solid 1.2 g (crude). Crude compound was purified by column chromatography on silica gel (230-400 mesh). Desired compound was eluted in 10% EtOAc in n-Hexane to get off white semi solid (0.54 g, 57.45%). 1H NMR (400 MHz, CDCl3) δ: 1.53 (s, 9H), 3.45 (d, J=17.2 Hz, 1H), 3.76-3.81 (m, 1H), 4.10-4.14 (m, 2H), 4.32 (d, J=9.88 Hz, 2H), 4.43 (d, J=16.88 Hz, 1H), 4.85-4.90 (m, 1H), 5.13 (s, 2H), 7.25 (m, 2H), 7.36-7.37 (m, 1H), 7.54 (d, J=7.96 Hz, 1H), 7.73 (s, 1H), 7.83 (d, J=7.68 Hz, 1H), LC-MS (m/z): 540.6 (M+H)

Workup

  1. customwas purged with nitrogen gas for 30 minutes
  2. additionTo this reaction mixture was added pre 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 completion of starting material, the reaction mixture was filtered through celite bed and bed
  8. washwas washed with 10% MeOH in DCM (30 mL)
  9. concentrationFiltrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-2f67c41eb6de4b81b6db2554539311bd
Source dataset
uspto-grants-2015_12
Patent number
US09221835B2

Reaction notes

Loading…