Water → 1-Benzhydryl-2-methylazetidin-3-yl methanesulfonate

HRID 1051680Notes

Reaction equation

HRID 1051680 reaction equation
[CH:1]([N:14]1[CH2:17][CH:16]([OH:18])[CH:15]1[CH3:19])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(NC(C)C)(C)C.[CH3:27][S:28](Cl)(=[O:30])=[O:29].O>ClCCl>[CH3:27][S:28]([O:18][CH:16]1[CH2:17][N:14]([CH:1]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH:15]1[CH3:19])(=[O:30])=[O:29]

Participants

6

Reactant 4

HCID 962WaterHCID 7912DiisopropylamineHCID 31297Methanesulfonyl chlorideHCID 14852479HCID 14852479, compound

Product 1

HCID 148524811-Benzhydryl-2-methylazetidin-3-yl methanesulfonateYield 29%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A 500-mL round-bottom flask was charged with 1-benzhydryl-2-methylazetidin-3-ol (15.0 g, 59.2 mmol), dichloromethane (30 mL), and N,N-diisopropylamine (21 mL, 160 mmol), and the solution was cooled to 0° C. A solution of methanesulfonyl chloride (6.2 mL, 77 mmol) in dichloromethane (10 mL) was added, and the resulting solution stirred overnight at room temperature. The reaction mixture was poured into 200 mL of water, and the aqueous phase was separated and extracted with dichloromethane (2×100 mL). The combined organic layers were washed with brine (2×100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 20:1, dichloromethane-ethyl acetate). The product was further purified by re-crystallization from hexane to afford 1-benzhydryl-2-methylazetidin-3-yl methanesulfonate (5.6 g, 29%) as a white solid. MS (ESI, pos. ion) m/z 332 [M+H]+.

Workup

  1. customthe aqueous phase was separated
  2. extractionextracted with dichloromethane (2×100 mL)
  3. washThe combined organic layers were washed with brine (2×100 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified via column chromatography on silica gel (eluting with 20:1, dichloromethane-ethyl acetate)
  8. customThe product was further purified by re-crystallization from hexane

Sources & evidence

ORD record
ord-d0946d026edd45189180890d6dd2e6af
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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