Diisopropylethylamine → (2R,3S,5R)-2-(2,2-Dimethylpropoxy)-5-formyl-3-methylmorpholine-4-carboxylic acid tert-butyl ester

HRID 20403

Reaction equation

HRID 20403 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:13]([CH2:14][OH:15])[CH2:12][O:11][C@@H:10]([O:16][CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[C@@H:9]1[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.S(=O)(=O)=O.N1C=CC=CC=1>ClCCl.CS(C)=O>[C:1]([O:5][C:6]([N:8]1[C@@H:13]([CH:14]=[O:15])[CH2:12][O:11][C@@H:10]([O:16][CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[C@@H:9]1[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 168533Sulfur trioxide-pyridineHCID 68563537(2R,3S,5S)-2-(2,2-Dimethylpropoxy)-5-hydroxymethyl-3-methylmorpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 58972240(2R,3S,5R)-2-(2,2-Dimethylpropoxy)-5-formyl-3-methylmorpholine-4-carboxylic acid tert-butyl esterYield 99.7%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

Add pyridine sulfur trioxide complex (0.42 g) to (2R,3S,5S)-2-(2,2-dimethylpropoxy)-5-hydroxymethyl-3-methylmorpholine-4-carboxylic acid tert-butyl ester (0.46 g, 1.45 mmol) and N,N-diisopropylethylamine (0.66 g, 5.07 mmol) in dichloromethane (1 mL) and dimethylsulfoxide (4 mL) at −2° C. and stir 30 minutes. TLC shows some alcohol remaining. Add more pyridine sulfur trioxide (100 mg) and stir 30 minutes. Pour into ice-cold saturated aqueous sodium chloride and extract with ethyl acetate. Wash the ethyl acetate layer with 1 N aqueous citric acid, saturated aqueous sodium chloride), dry (magnesium sulfate), filter and concentrate to give the title compound as an oil (456 mg).

Workup

  1. stirringstir 30 minutes
  2. additionPour into ice-cold saturated aqueous sodium chloride
  3. extractionextract with ethyl acetate
  4. washWash the ethyl acetate layer with 1 N aqueous citric acid, saturated aqueous sodium chloride),
  5. dry with materialdry (magnesium sulfate)
  6. filtrationfilter
  7. concentrationconcentrate

Sources & evidence

ORD record
ord-3e48c768ad554b59a51e4f94284c503d
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Linked notes

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