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

HRID 1508302Notes

Reaction equation

HRID 1508302 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]([C:32]([F:35])([F:34])[F:33])=[CH: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:12])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[N+:36]([CH3:39])([O-:38])=[O:37].C1CCN2C(=NCCC2)CC1>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]([CH2:39][N+:36]([O-:38])=[O:37])([C:32]([F:33])([F:35])[F:34])[CH2:10][C:11]([C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[C:18]2([CH2:22][N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:24]2)[O:17][CH2:16]3)=[O:12])[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

5

Reactant 3

HCID 6375NitromethaneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 90001161tert-butyl 5'-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-2-enoyl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

Product 1

HCID 89994541tert-butyl 5'-(3-(3,5-dichlorophenyl)-4,4,4-trifluoro-3-(nitromethyl)butanoyl)-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylateYield 91.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of tert-butyl 5′-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-2-enoyl)-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate (Preparation 10, 1 g, 1.89 mmol) in acetonitrile (10 mL) was added nitromethane (1.013 mL, 18.93 mmol) and DBU (0.275 mL, 1.84 mmol) at room temperature. Resulting reaction mixture was stirred at room temperature for 16 hours. After consumption of starting material; reaction mixture was quenched with water (25 mL) and extracted with ethyl acetate (2×25 mL). Combined organic layers were washed with brine (60 mL), dried over sodium sulfate and concentrated under reduced pressure to get brown semi solid (1.41 g, crude). Crude compound was purified by column chromatography using silica gel (230-400 mesh). Desired compound was eluted in 10% ethyl acetate in n-hexane to get light yellow sticky liquid (1.02 g, 91.07%). 1H NMR (400 MHz, CDCl3) δ: 1.47 (s, 9H), 3.97 (d, J=18.64 Hz, 1H), 4.10-4.17 (m, 3H), 4.34 (d, J=9.8 Hz, 2H), 5.16 (s, 2H), 5.45 (d, J=12.32 Hz, 1H), 5.58 (d, J=12.36 Hz, 1H), 7.18 (s, 2H), 7.40-7.41 (m, 1H), 7.61 (d, J=7.92 Hz, 1H), 7.81 (s, 1H), 7.98-8.00 (m, 1H), LC-MS (m/z): 587.1 (M−H).

Workup

  1. customResulting
  2. customreaction mixture
  3. customAfter consumption of starting material
  4. customreaction mixture
  5. customwas quenched with water (25 mL)
  6. extractionextracted with ethyl acetate (2×25 mL)
  7. washCombined organic layers were washed with brine (60 mL)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customto get brown semi solid (1.41 g, crude)
  11. customCrude compound was purified by column chromatography
  12. washDesired compound was eluted in 10% ethyl acetate in n-hexane

Sources & evidence

ORD record
ord-a51d3613b53d465aa67dfc5bfe77652e
Source dataset
uspto-grants-2015_12
Patent number
US09221835B2

Reaction notes

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