反応式
Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[F:11].C([Li])CCC.[C:17]1(=[O:22])[CH2:21][CH2:20][CH2:19][CH2:18]1>O1CCCC1.[NH4+].[Cl-].Cl>[F:11][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:2]=1[C:17]1([OH:22])[CH2:21][CH2:20][CH2:19][CH2:18]1)[C:6]([OH:8])=[O:7]参加物
反応条件
- 温度
- -70 °C
実験手順
4-Bromo-3-fluoro-benzoic acid (3.00 g, 13.7 mmol) was dissolved in tetrahydrofuran (60 mL) and the solution was cooled to −78° C. n-Butyllithium (18.8 mL of 1.6 M in hexanes, 30 mmol) was added dropwise over 20 min while maintaining the internal temperature under −70° C. The reaction mixture was allowed to stir for 30 min at −78° C. and then cyclopentanone (1.21 mL, 13.7 mmol) was added in a dropwise while maintaining the internal temperature below −70° C. The mixture was stirred at −78° C. for 30 min the allowed to warm to room temperature. The reaction mixture was diluted with saturated NH4Cl (50 mL) and 1 M HCl (25 mL) and extracted with dichloromethane (3×50 mL). The combined extracts were dried over Na2SO4 and concentrated in vacuo. Silica gel chromatography (0-5% methanol/dichloromethane) provided 3-fluoro-4-(1-hydroxycyclopentyl)benzoic acid (400 mg, 13%) as a white solid. ESI-MS m/z calc. 224.1. Found 225.3 (M+1)+; Retention time: 1.16 minutes (3 min run). 1H NMR (400 MHz, DMSO-d6) δ 13.12 (s, 1H), 7.80-7.70 (m, 2H), 7.60-7.51 (m, 1H), 5.13 (s, 1H), 2.08-1.95 (m, 2H), 1.95-1.81 (m, 4H), 1.81-1.67 (m, 2H).
後処理
- additionwas added dropwise over 20 min
- temperaturewhile maintaining the internal temperature below −70° C
- stirringThe mixture was stirred at −78° C. for 30 min the
- temperatureto warm to room temperature
- extractionextracted with dichloromethane (3×50 mL)
- dry with materialThe combined extracts were dried over Na2SO4
- concentrationconcentrated in vacuo
出典と根拠
- ORDレコード
- ord-2e3aa8f578624df6bc9fa709ef0bd6b7
- 出典データセット
- uspto-grants-2014_09
- 特許番号
- US08828996B2
関連ノート
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