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

HRID 1039103Notes

Reaction equation

HRID 1039103 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([CH:14]3[CH2:16][CH:15]3[CH2:17][CH2:18][OH:19])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[S:20](Cl)([C:23]1[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=1)(=[O:22])=[O:21]>ClCCl.CN(C1C=CN=CC=1)C>[CH3:27][C:26]1[CH:28]=[CH:29][C:23]([S:20]([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:22])=[O:21])=[CH:24][CH:25]=1

Participants

5

Reactant 2

HCID 73974-Toluenesulfonyl chloride2×HCID 581284692-{2-[1-(5-Chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol

Product 1

HCID 866661472-{(1R,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl 4-methylbenzenesulfonate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

The title compound was synthesized using 2-{2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol from Example 2b-S (slow) (41.2 mg, 0.146 mmol) was in 1.46 mL dichloromethane. TEA (0.0408 mL, 0.296 mol), DMAP (1.786 mg, 0.015 mmol) and TsCl (33.5 mg, 0.175 mmol) were sequentially added. The mixture was stirred at room temperature for 3 hour. Another 0.02 mL of TEA, 1 mg of DMAP and 14 mg of TsCl were added. Reaction mixture was stirred at room temperature for 30 min. The mixture was poured in to ice water. The aqueous phase was extracted with ethyl acetate for 3 times. The combined organic layers were washed with water and brine, then dried over Na2SO4 and concentrated. The residue was purified by column chromatography using gradient elution (0 to 50% ethyl acetate in hexane) to give the titled compound.

Workup

  1. customThe title compound was synthesized
  2. customReaction mixture
  3. stirringwas stirred at room temperature for 30 min
  4. extractionThe aqueous phase was extracted with ethyl acetate for 3 times
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography
  9. washelution (0 to 50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-d90fba47014d41999a9c3764a0f87621
Source dataset
uspto-grants-2013_10
Patent number
US08552022B2

Reaction notes

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