Methanesulfonyl chloride → (R)-Phenyl{(2S)-4-[(1R)-1-phenylethyl]morpholin-2-yl}methyl methanesulphonate

HRID 131186Notes

Reaction equation

HRID 131186 reaction equation
[C:1]1([C@H:7]([C@H:9]2[O:14][CH2:13][CH2:12][N:11]([C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:16])[CH2:10]2)[OH:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.[CH3:32][S:33](Cl)(=[O:35])=[O:34]>ClCCl>[CH3:32][S:33]([O:8][C@H:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C@H:9]1[O:14][CH2:13][CH2:12][N:11]([C@@H:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:16])[CH2:10]1)(=[O:35])=[O:34]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 59732175(R)-Phenyl{(2S)-4-[(1R)-1-phenylethyl]morpholin-2-yl}methanol

Product 1

HCID 59732174(R)-Phenyl{(2S)-4-[(1R)-1-phenylethyl]morpholin-2-yl}methyl methanesulphonateYield 55%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 50 (0.05 g, 0.17 mmol) in dichloromethane (1 ml) at room temperature was added polymer supported Hünig's base ((Argonaut, 3.56 mmol/g, 0.089 g, 0.32 mmol, 1.9 eq) and methanesulphonyl chloride (0.02 g, 0.19 mmol). The mixture was stirred under nitrogen for 6 hours then filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (eluent: ethyl acetate/heptane 33/67 (v/v)) to give 51 as a colourless oil (0.035 g, 55%%); MW 375.49; C20H25NO4S 1H NMR (CDCl3) 7.20-7.35 (10H, m), 5.46 (1H, d), 3.79-3.88 (2H, m), 3.59 (1H,td), 3.4 (1H, q), 2.68-2.78 (2H, m), 2.68 (3H, s), 2.03-2.24 (2H, m), 1.34 (3H, d). m/z [M+H]+ 376.

Workup

  1. filtrationthen filtered
  2. concentrationconcentrated in vacuo
  3. customThe crude product was purified by flash column chromatography (eluent: ethyl acetate/heptane 33/67 (v/v))

Sources & evidence

ORD record
ord-a2372205336f4c768df13537a2c8f2e9
Source dataset
uspto-grants-2008_06
Patent number
US07384941B2

Reaction notes

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