4-Toluenesulfonyl chloride → tert-Butyl (3R)-6-cyclohexyl-3-[3-({[(4-methylphenyl)sulfonyl]oxy}methyl)1,2,4-oxadiazol-5-yl]hexanoate

HRID 1350284Notes

Reaction equation

HRID 1350284 reaction equation
[H-].[Na+].[CH:3]1([CH2:9][CH2:10][CH2:11][C@@H:12]([C:21]2[O:25][N:24]=[C:23]([CH2:26][OH:27])[N:22]=2)[CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.[C:28]1([CH3:38])[CH:33]=[CH:32][C:31]([S:34](Cl)(=[O:36])=[O:35])=[CH:30][CH:29]=1>O1CCCC1>[CH:3]1([CH2:9][CH2:10][CH2:11][C@@H:12]([C:21]2[O:25][N:24]=[C:23]([CH2:26][O:27][S:34]([C:31]3[CH:32]=[CH:33][C:28]([CH3:38])=[CH:29][CH:30]=3)(=[O:36])=[O:35])[N:22]=2)[CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 59909744tert-Butyl(3R)-6-cyclohexyl-3-[3-(hydroxymethyl)-1,2,4-oxadiazol-5-yl]hexanoate

Product 1

HCID 16747945tert-Butyl (3R)-6-cyclohexyl-3-[3-({[(4-methylphenyl)sulfonyl]oxy}methyl)1,2,4-oxadiazol-5-yl]hexanoateYield 55.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of sodium hydride 60% suspension in mineral oil (1.52 g, 38.00 mmol) in anhydrous tetrahydrofuran (30 ml) was cooled to 0° C. and treated with a solution of tert-butyl (3R)-6-cyclohexyl-3-[3-(hydroxymethyl)-1,2,4-oxadiazol-5-yl]hexanoate (Preparation 176) (13.40 g, 38.00 mmol) in anhydrous tetrahydrofuran (120 ml) and stirred under a nitrogen atmosphere for 30 minutes. p-Toluene sulphonyl chloride (7.25 g, 38.00 mmol) was added portionwise and the mixture was allowed to warm to room temperature over 18 hours. The solvent was removed under reduced pressure The residue was dissolved in ethyl acetate and washed with water, saturated sodium hydrogen carbonate solution and brine, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The oil was purified by column chromatography on silica gel eluting with dichloromethane to afford the title compound (10.75 g).

Workup

  1. temperatureto warm to room temperature over 18 hours
  2. customThe solvent was removed under reduced pressure The residue
  3. dissolutionwas dissolved in ethyl acetate
  4. washwashed with water, saturated sodium hydrogen carbonate solution and brine
  5. dry with materialdried over anhydrous sodium sulphate
  6. filtrationfiltered
  7. customthe solvent removed under reduced pressure
  8. customThe oil was purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-26809a154369491a89f48d8ab28dea31
Source dataset
uspto-grants-2007_05
Patent number
US07214694B2

Reaction notes

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