Potassium Fluoride → 2-Fluoro-3-(pyrrolidin-1-ylmethyl)phenol

HRID 1159397ノート

反応式

HRID 1159397 の反応式
[Si]([O:8][C:9]1[C:10]([F:21])=[C:11]([CH:18]=[CH:19][CH:20]=1)[CH2:12][N:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1)(C(C)(C)C)(C)C.[F-].[K+]>CO>[F:21][C:10]1[C:11]([CH2:12][N:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[CH:18][CH:19]=[CH:20][C:9]=1[OH:8]

参加物

4

反応物 2

HCID 522689Potassium FluorideHCID 686193431-(3-{[Tert-butyl(dimethyl)silyl]oxy}-2-fluorobenzyl)pyrrolidine

生成物 1

HCID 686193012-Fluoro-3-(pyrrolidin-1-ylmethyl)phenol収率 80%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

To a solution of intermediate 33, 1-(3-{[tert-butyl(dimethyl)silyl]oxy}-2-fluorobenzyl)pyrrolidine (19 g, 60 mmol) in MeOH (200 mL) was added KF (7.1 g, 120 mmol), and the mixture was stirred at RT for 1 h. The reaction mixture evaporated in vacuo. Water (100 mL) and concentrated HCl were added to attain pH˜6. The organic layer was separated. The aqueous one was extracted with CH2Cl2 (2×100 mL). The organic layers were discarded. The aqueous fraction was alkalized with K2CO3 to pH˜10, the aqueous one was extracted with CHCl3. The organic layer was washed with brine, dried over Na2SO4 and evaporated in vacuo, recrystallized from Et2O/hexane mixture (1:1) to give the title compound (9.3 g, 78%, 48 mmol) as a yellow crystals. LCMS data: 197.1 and 196.1 (M+H)+ (calculated for C11H14FNO 195.24). 1H NMR data (DMSO-d6): 9.63 (s, 1H, OH), 6.87-6.96 (m, 1H, H—Ar), 6.71-6.85 (m, 2H, H—Ar), 3.58 (s, 2H, Ar—CH2); 2.36-2.46 (m, 4H), 1.61-1.72 (m, 4H).

後処理

  1. customThe reaction mixture evaporated in vacuo
  2. additionWater (100 mL) and concentrated HCl were added
  3. customThe organic layer was separated
  4. extractionThe aqueous one was extracted with CH2Cl2 (2×100 mL)
  5. extractionthe aqueous one was extracted with CHCl3
  6. washThe organic layer was washed with brine
  7. dry with materialdried over Na2SO4
  8. customevaporated in vacuo
  9. customrecrystallized from Et2O/hexane mixture (1:1)

出典と根拠

ORDレコード
ord-c1acc92669294f71aec307874443fd09
出典データセット
uspto-grants-2010_10
特許番号
US07812040B2

反応ノート

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