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 1508302ノート

反応式

HRID 1508302 の反応式
[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

参加物

5

反応物 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

生成物 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収率 91.6%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-a51d3613b53d465aa67dfc5bfe77652e
出典データセット
uspto-grants-2015_12
特許番号
US09221835B2

反応ノート

読み込み中…