Pyridine → Trifluoromethanesulfonic acid 3-chloro-5-methoxy-4-piperidin-1-ylmethylphenyl ester

HRID 1505891Notes

Reaction equation

HRID 1505891 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:17])[CH:5]=[C:6]([O:15][CH3:16])[C:7]=1[CH2:8][N:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.N1C=CC=CC=1.[F:24][C:25]([F:31])([F:30])[S:26](Cl)(=[O:28])=[O:27]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([O:17][S:26]([C:25]([F:31])([F:30])[F:24])(=[O:28])=[O:27])[CH:5]=[C:6]([O:15][CH3:16])[C:7]=1[CH2:8][N:9]1[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 79000Trifluoromethanesulfonyl chlorideHCID 582668253-Chloro-5-methoxy-4-piperidin-1-ylmethylphenol

Product 1

HCID 58266343Trifluoromethanesulfonic acid 3-chloro-5-methoxy-4-piperidin-1-ylmethylphenyl esterYield 101.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 3-chloro-5-methoxy-4-piperidin-1-ylmethylphenol (223 mg, 0.87 mmol) and pyridine (0.28 mL, 3.5 mmol) in DCM (10 mL) at −20° C. was added trifluoromethanesulfonyl chloride (0.29 mL, 1.7 mmol). After the addition was complete the reaction mixture was allowed to warm to ambient temperature then diluted with DCM (20 mL) then washed with water (10 mL). The organic phase was separated, dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to afford an oil that was purified by flash chromatography (silica, 12 g column, ISCO, 0-100% ethyl acetate in cyclohexane) to afford the title compound as a red oil (341 mg, 73%). 1H NMR (CDCl3, 300 MHz): 7.06 (d, J=2.3 Hz, 1H), 6.85 (d, J=2.3 Hz, 1H), 4.40 (s, 2H), 4.05 (s, 3H), 3.72-3.42 (m, 1H), 3.06-2.72 (m, 1H), 2.23-1.75 (m, 4H), 1.73-1.36 (m, 4H).

Workup

  1. additionAfter the addition
  2. washthen washed with water (10 mL)
  3. customThe organic phase was separated
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford an oil that
  8. customwas purified by flash chromatography (silica, 12 g column, ISCO, 0-100% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-6e459515fb0e4738b725e885fce6c7aa
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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