Water → (R)-tert-butyl 3-((R)-(3-chlorophenyl)(2-(methylsulfonyloxy)ethoxy)methyl)piperidine-1-carboxylate

HRID 218372Notes

Reaction equation

HRID 218372 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([O:22][CH2:23][CH2:24][OH:25])[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.[CH3:33][S:34](Cl)(=[O:36])=[O:35].O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([O:22][CH2:23][CH2:24][O:25][S:34]([CH3:33])(=[O:36])=[O:35])[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:20])([CH3:21])[CH3:19])=[O:16])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 58017426(R)-tert-butyl 3-((R)-(3-chlorophenyl)(2-hydroxyethoxy)methyl)piperidine-1-carboxylate

Product 1

HCID 58017416(R)-tert-butyl 3-((R)-(3-chlorophenyl)(2-(methylsulfonyloxy)ethoxy)methyl)piperidine-1-carboxylateYield 98.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (R)-tert-butyl 3-((R)-(3-chlorophenyl)(2-hydroxyethoxy)methyl)piperidine-1-carboxylate (12.50 g, 34 mmol) in dry CH2Cl2 (150 mL) was added Et3N (13.74 g, 18.3 mL, 136 mmol, 4 eq) at −5-0° C. Then a solution of MsCl (7.75 g, 5.16 mL, 68 mmol, 2 eq) in dry CH2Cl2 (50 mL) was added dropwise at the same temperature. After addition, it was allowed to warm to rt gradually. Upon reaction completion water (100 mL) was added. The aqueous layer was extracted with CH2Cl2 (3×80 mL), the combined organic layers was washed with 10% citric acid, sat. NaHCO3 and brine, then dried over Na2SO4, filtered and concentrated to give (R)-tert-butyl 3-((R)-(3-chlorophenyl)(2-(methylsulfonyloxy)ethoxy)methyl)piperidine-1-carboxylate (15 g), which was used in the next step without purification.

Workup

  1. additionAfter addition, it
  2. additionwas added
  3. extractionThe aqueous layer was extracted with CH2Cl2 (3×80 mL)
  4. washthe combined organic layers was washed with 10% citric acid, sat. NaHCO3 and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-c021541140e7438cb2ab4d14c5376749
Source dataset
uspto-grants-2012_06
Patent number
US08198453B2

Reaction notes

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