4-Toluenesulfonyl chloride → 2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl 4-methylbenzenesulfonate

HRID 1039051Notes

Reaction equation

HRID 1039051 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C@H:14]3[CH2:16][C@H:15]3[CH2:17][CH2:18][OH:19])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.C(N(CC)CC)C.[S:27](Cl)([C:30]1[CH:36]=[CH:35][C:33]([CH3:34])=[CH:32][CH:31]=1)(=[O:29])=[O:28]>ClCCl.CN(C)C1C=CN=CC=1>[CH3:34][C:33]1[CH:35]=[CH:36][C:30]([S:27]([O:19][CH2:18][CH2:17][C@@H:15]2[CH2:16][C@@H:14]2[CH:11]2[CH2:12][CH2:13][N:8]([C:5]3[N:6]=[CH:7][C:2]([Cl:1])=[CH:3][N:4]=3)[CH2:9][CH2:10]2)(=[O:29])=[O:28])=[CH:31][CH:32]=1

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 581286112-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol

Product 1

HCID 866661412-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl 4-methylbenzenesulfonate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol (176 mg, 0.63 mmol) from. Step 6, Example 2 was dissolved in dichloromethane (3 mL), then added triethylamine (190 mg, 1.87 mmol), 4-dimethylaminopyridine (15.3 mg, 0.13 mmol), last tosylchloride (167 mg, 0.87 mmol), stirred under N2 for 1.5 hours. The reaction solution was poured into ice water (10 mL), extracted with dichloromethane (10 mL×2). The organic phase was combined and dried by magnesium sulfate, filtered, then concentrated and purified by column chromatography through a 24 gram RediSep Rf™ silica gel cartridge eluting with 10% ethyl acetate/hexanes to give the title compound as a white solid.

Workup

  1. extractionextracted with dichloromethane (10 mL×2)
  2. dry with materialdried by magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by column chromatography through a 24 gram RediSep Rf™ silica gel cartridge
  6. washeluting with 10% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-c065f254d2464eef8d3dfedb625ff85c
Source dataset
uspto-grants-2013_10
Patent number
US08552022B2

Reaction notes

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