4-Methylmorpholine → 4-(4-Hydroxy-benzenesulfonyl)-2,2-dimethyl-thiomorpholine-3-carboxylic acid methyl ester

HRID 1976475Notes

Reaction equation

HRID 1976475 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.[CH3:24][C:25]1([CH3:35])[S:30][CH2:29][CH2:28][NH:27][C@H:26]1[C:31]([O:33][CH3:34])=[O:32].CN1CCOCC1>C(Cl)(Cl)Cl.C(OCC)(=O)C.CO>[CH3:34][O:33][C:31]([CH:26]1[C:25]([CH3:35])([CH3:24])[S:30][CH2:29][CH2:28][N:27]1[S:8]([C:5]1[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=1)(=[O:10])=[O:9])=[O:32]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 114240934-Hydroxybenzene-1-sulfonyl chlorideHCID 18345630methyl (3S)-2,2-dimethylthiomorpholine-3-carboxylate

Product 1

HCID 227319314-(4-Hydroxy-benzenesulfonyl)-2,2-dimethyl-thiomorpholine-3-carboxylic acid methyl esterYield 83.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6212ChloroformSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.5 g (2.6 mmol) of 4-hydroxybenzenesulfonyl chloride (J. Org. Chem. 1973, 38, 1047) in 5 mL of chloroform at room temperature was added 0.706 mL (2.86 mmol) of N,O-bis(trimethylsilyl)acetamide. The reaction mixture was stirred for 1 h and added a solution of 0.41 g (2.16 mmol) of methyl (3S)-2,2-dimethyl-3-thiomorpholinecarboxylate in 1 mL of chloroform in one portion, followed by 0.48 mL (4.37 mmol) of N-methylmorpholine. The resulting mixture was stirred for 18 h and 10 mL of methanol was added and the resulting mixture was heated to reflux for 1 h. The reaction was diluted with ethyl acetate, washed with water, 5% HCl and brine, dried over MgSO4 filtered and concentrated in vacuo. The residue was triturated with ether:hexanes (1:2) to provide 0.62 g (83%) of 4-(4-hydroxy-benzenesulfonyl)-2,2-dimethyl-thiomorpholine-3- carboxylic acid methyl ester as a pale yellow solid. Electrospray Mass Spec: 344.4 (M−H)−

Workup

  1. stirringThe resulting mixture was stirred for 18 h
  2. temperaturethe resulting mixture was heated
  3. temperatureto reflux for 1 h
  4. washwashed with water, 5% HCl and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was triturated with ether:hexanes (1:2)

Sources & evidence

ORD record
ord-ef3f6557e4f34db19cc337e54632ae3d
Source dataset
uspto-grants-2001_05
Patent number
US06225311B1

Reaction notes

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