Methanesulfonyl chloride → HCID 86591982, compound

HRID 1358026Notes

Reaction equation

HRID 1358026 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([OH:18])[CH:14]=3)[CH:9]2[CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][NH:30]3)=[CH:22][CH:21]=2)=[CH:4][CH:3]=1.[CH3:35][S:36](Cl)(=[O:38])=[O:37]>N1C=CC=CC=1>[CH3:35][S:36]([O:18][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[CH:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][NH:30]3)=[CH:22][CH:21]=1)[N:8]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[CH2:17][CH2:16]2)(=[O:38])=[O:37]

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 54107592HCID 54107592, compound

Product 1

HCID 86591982HCID 86591982, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution containing 2-(4-fluorophenyl)-1-{4-[(2-piperidyl)ethoxy]benzyl}-1,2,3,4-tetrahydroisoquinolin-6-ol (0.100 g, 0.2 mmol) in pyridine (0.4 ml) was added methyl sulfonyl chloride (25 μl, 0.32 mmol). After stirring for five hours, solvent was removed and the reaction was basified with aqueous sodium bicarbonate solution. The reaction was extracted with dichloromethane and concentrated. The product was purified by semipreparative HLPC (C-18 column, 10-100% acetonitrile/water with 0.1% trifluoroacetic acid). The acetonitrile was removed from the HPLC fractions containing the desired product. Ethyl acetate was added and the solution neutralized using saturated sodium bicarbonate. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated to provide the title compound (0.0135 g, 13% yield): 1H NMR (CDCl3) 6.7-7.1 (m, 11H), 4.78 (t, 1H), 4.1 (t, 3H), 3.45-3.62 (m, 2H), 2.62-3.18 (m, 8H), 2.58 (m, 4H), 1.63 (m, 4H), 1.43 (m, 2H); ES-MS (m/z) 539 [M+H]+.

Workup

  1. customsolvent was removed
  2. extractionThe reaction was extracted with dichloromethane
  3. concentrationconcentrated
  4. customThe product was purified by semipreparative HLPC (C-18 column, 10-100% acetonitrile/water with 0.1% trifluoroacetic acid)
  5. customThe acetonitrile was removed from the HPLC fractions
  6. additioncontaining the desired product
  7. additionEthyl acetate was added
  8. washThe organic layer was washed with brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-76668da40fff4255aebc533f17c697d9
Source dataset
uspto-grants-2003_07
Patent number
US06593322B1

Reaction notes

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