Triethylamine → Methanesulfonic Acid trans-4-(Benzyl-methyl-amino)-1-[2-(4-fluorophenyl)-ethyl]-piperidin-3-ylmethyl Ester

HRID 896554Notes

Reaction equation

HRID 896554 reaction equation
[CH2:1]([N:8]([CH3:26])[CH:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH2:11][CH:10]1[CH2:24][OH:25])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:34][S:35](Cl)(=[O:37])=[O:36]>ClCCl>[CH2:1]([N:8]([CH3:26])[C@@H:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH2:11][C@H:10]1[CH2:24][O:25][S:35]([CH3:34])(=[O:37])=[O:36])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 22350215{4-(Benzyl-methyl-amino)-1-[2-(4-fluorophenyl)-ethyl]-piperidin-3-yl}-methanol

Product 1

HCID 86591724Methanesulfonic Acid trans-4-(Benzyl-methyl-amino)-1-[2-(4-fluorophenyl)-ethyl]-piperidin-3-ylmethyl EsterYield 108.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of -{4-(benzyl-methyl-amino)-1-[2-(4-fluorophenyl)-ethyl]-piperidin-3-yl}-methanol (105 mg, 294 μmol) and triethylamine (62 μL, 442 μmol) in dichloromethane (1 mL) was stirred on an ice bath and treated with a solution of methanesulfonyl chloride (25 μL, 320 μmol) in dichloromethane (0.5 mL). After 1.75 hours, the mixture was concentrated and the residue was dissolved in ethyl acetate. The suspension was filtered, the solid was rinsed with ethyl acetate, and the filtrate was concentrated under vacuum to provide a yellowish gum (139 mg) which was used without purification. 1H NMR (300 MHz, CDCl3) δ7.32 (m, 5H), 7.17 (m, 2H), 6.99 (t, J=9 Hz, 2H), 4.57 (dd, J=10, 3 Hz, 1H), 4.29 (m, 1H), 3.72 (d, J=13 Hz, 1H), 3.50 (d, J=13 Hz, 1H), 3.4-3.1 (m, 2H), 3.00 (s, 3H), 2.83 (m, 2H), 2.70 (m, 2H), 2.48 (m, 1H), 2.35 (m, 1H), 2.22 (s, 3H), 2.07 (m, 2H), 2.0-1.7 (m, 2H).

Workup

  1. concentrationthe mixture was concentrated
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. filtrationThe suspension was filtered
  4. washthe solid was rinsed with ethyl acetate
  5. concentrationthe filtrate was concentrated under vacuum

Sources & evidence

ORD record
ord-ec17fc40ce884d25abe4809c29ebf951
Source dataset
uspto-grants-2005_07
Patent number
US06919356B2

Reaction notes

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