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

HRID 1888428Notes

Reaction equation

HRID 1888428 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-87bbda0d87044a04be2a5b8607d49c62
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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