Sodium hydride → HCID 66918675, compound

HRID 1367544Notes

Reaction equation

HRID 1367544 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[SH:8].[H-].[Na+].C([O:13][C:14]([C@@H:16]1[CH2:20][C@@H:19](OS(C)(=O)=O)[CH2:18][C@H:17]1[CH2:26][N:27]1[CH2:32][CH2:31][CH:30]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[CH2:29][CH2:28]1)=[O:15])C>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8][C@H:19]1[CH2:20][C@@H:16]([C:14]([OH:15])=[O:13])[C@H:17]([CH2:26][N:27]2[CH2:28][CH2:29][CH:30]([C:33]3[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=3)[CH2:31][CH2:32]2)[CH2:18]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 80599o-ChlorothiophenolHCID 86649031HCID 86649031, compound

Product 1

HCID 66918675HCID 66918675, compoundYield 16.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-chlorobenzenethiol (141 mg) in tetrahydrofuran (2 mL) was added sodium hydride (dispersion in oil, 55% w/w, 50 mg). The mixture was stirred 20 min at room temperature. Then the mixture was cooled down to 0° C. and a solution of (1R,2R,4S)-2-[4-(4-Fluoro-phenyl)-piperidin-1-ylmethyl]-4-methanesulfonyloxy-cyclopentanecarboxylic acid ethyl ester (example 148 step 4, 180 mg) in tetrahydrofuran (2 mL) was added dropwise. The reaction mixture was stirred at room temperature over 24 h then partitioned between hydrochloric acid (1N) and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with a saturated aqueous solution of sodium carbonate and brine then dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with a gradient of dichloromethane:methanol (98:2 to 9:1 v/v) as eluant to afford the title compound (31 mg, 16%) as a light brown solid. MS (EI): 448.1 (M+H)+.

Workup

  1. temperatureThen the mixture was cooled down to 0° C.
  2. stirringThe reaction mixture was stirred at room temperature over 24 h
  3. customthen partitioned between hydrochloric acid (1N) and ethyl acetate
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washthe combined organic layers were washed with a saturated aqueous solution of sodium carbonate and brine
  6. dry with materialthen dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography on silica gel with a gradient of dichloromethane:methanol (98:2 to 9:1 v/v) as eluant

Sources & evidence

ORD record
ord-859e2ddc9d51483ca28f76a6106bd5f5
Source dataset
uspto-grants-2011_02
Patent number
US07893099B2

Reaction notes

Loading…