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

HRID 1508293Notes

Reaction equation

HRID 1508293 reaction equation
[F:1][C:2]([F:40])([F:39])[C:3]([CH2:35][N+:36]([O-])=O)([C:26]1[CH:31]=[C:30]([Cl:32])[C:29]([Cl:33])=[C:28]([Cl:34])[CH:27]=1)[CH2:4][C:5]([C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[C:12]1([CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]1)[O:11][CH2:10]2)=O>C(O)C>[Cl:34][C:28]1[CH:27]=[C:26]([C:3]2([C:2]([F:40])([F:39])[F:1])[CH2:4][C:5]([C:7]3[CH:8]=[C:9]4[C:13](=[CH:14][CH:15]=3)[C:12]3([CH2:16][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:20])[CH2:18]3)[O:11][CH2:10]4)=[N:36][CH2:35]2)[CH:31]=[C:30]([Cl:32])[C:29]=1[Cl:33]

Participants

3

Reactant 1

HCID 90001283tert-butyl 5'-(4,4,4-trifluoro-3-(nitromethyl)-3-(3,4,5-trichlorophenyl)butanoyl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

Product 1

HCID 89994582tert-butyl 5'-(3-(3,4,5-trichlorophenyl)-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

A solution of tert-butyl 5′-(4,4,4-trifluoro-3-(nitromethyl)-3-(3,4,5-trichlorophenyl)butanoyl)-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate (Preparation 3, 5.1 g, 8.97 mmol) in ethanol (51 mL) was purged with nitrogen gas for 30 minutes. To this reaction mixture was added pre-washed Raney Nickel (1.22 g, 50% suspension in water). Reaction mixture was stirred under hydrogen atmosphere using balloon for 16 hours at room temperature. Progress of the reaction was monitored by TLC. After consumption of intermediate-4, reaction mixture was filtered through celite bed, the bed was washed with 10% MeOH in DCM (30 mL). The filtrate was concentrated to get 4 g off white solid as crude mass, crude was purified by column chromatography on silica gel using 230-400 silica mesh. Desired product was eluted in 8% ethyl acetate in n-Hexane to get 1.6 g off white semi-solid as desired product and 1.5 g of starting material was recovered. 1H NMR (400 MHz, CDCl3) δ: 1.47 (s, 9H), 3.43 (d, J=17.52 Hz, 1H), 3.76-3.81 (m, 1H), 4.13 (d, J=9.64 Hz, 2H), 4.32 (d, J=9.56 Hz, 2H), 4.42 (d, J=17.12 Hz 1H), 4.87 (d, J=17.12 Hz, 1H), 5.13 (s, 2H), 7.39 (s, 2H), 7.54 (d, J=7.92 Hz, 1H), 7.73 (s, 1H), 7.83 (d, J=7.92 Hz, 1H).

Workup

  1. additionTo this reaction mixture was added
  2. washpre-washed Raney Nickel (1.22 g, 50% suspension in water)
  3. customReaction mixture
  4. customfor 16 hours
  5. customat room temperature
  6. customAfter consumption of intermediate-4, reaction mixture
  7. filtrationwas filtered through celite bed
  8. washthe bed was washed with 10% MeOH in DCM (30 mL)
  9. concentrationThe filtrate was concentrated
  10. customto get 4 g off white solid as crude mass, crude
  11. customwas purified by column chromatography on silica gel using 230-400 silica
  12. washDesired product was eluted in 8% ethyl acetate in n-Hexane

Sources & evidence

ORD record
ord-56d2d3acba91494196fd9c335544d97c
Source dataset
uspto-grants-2015_12
Patent number
US09221835B2

Reaction notes

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