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

HRID 1159397Notes

Reaction equation

HRID 1159397 reaction equation
[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]

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-c1acc92669294f71aec307874443fd09
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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