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

HRID 1505894Notes

Reaction equation

HRID 1505894 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([OH:17])[CH:6]=[C:7]([CH3:16])[C:8]=1[CH2:9][N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.N1C=CC=CC=1.[F:24][C:25]([F:31])([F:30])[S:26](Cl)(=[O:28])=[O:27]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:17][S:26]([C:25]([F:31])([F:30])[F:24])(=[O:28])=[O:27])[CH:6]=[C:7]([CH3:16])[C:8]=1[CH2:9][N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 79000Trifluoromethanesulfonyl chlorideHCID 582664193-Methoxy-5-methyl-4-piperidin-1-ylmethylphenol

Product 1

HCID 58266639Trifluoromethanesulfonic acid 3-methoxy-5-methyl-4-piperidin-1-ylmethylphenyl esterYield 79.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution 3-methoxy-5-methyl-4-piperidin-1-ylmethylphenol (563 mg, 2.4 mmol) and pyridine (0.77 mL, 10.0 mmol) in DCM (20 mL) at 0° C. was added trifluoromethanesulfonyl chloride (0.81 mL, 4.8 mmol). After the addition was complete the reaction was allowed to warm to ambient temperature. The mixture was diluted with DCM (20 mL) and 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, 40 g column, ISCO, 0-100% ethyl acetate in cyclohexane) to afford the title compound as a red oil (698 mg, 58%). NMR (CDCl3, 300 MHz): 6.82 (d, J=2.4 Hz, 1H), 6.73 (d, J=2.4 Hz, 1H), 4.28 (s, 2H), 3.96 (s, 3H), 3.67-3.35 (m, 1H), 2.99-2.66 (m, 1H), 2.47 (s, 3H), 2.21-1.75 (m, 4H), 1.73-1.35 (m, 4H).

Workup

  1. additionAfter the addition
  2. washwashed 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, 40 g column, ISCO, 0-100% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-591ab1794bdb41c4b5de8c68e6e42e56
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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