Dimethyl Sulfoxide → tert-butyl N-[(1-formylcyclopropyl)methyl]carbamate

HRID 1848349Notes

Reaction equation

HRID 1848349 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:15][C:16](=[O:24])[NH:17][CH2:18][C:19]1([CH2:22][OH:23])[CH2:21][CH2:20]1)([CH3:14])([CH3:13])[CH3:12].CCN(CC)CC>C(Cl)Cl.O>[C:11]([O:15][C:16](=[O:24])[NH:17][CH2:18][C:19]1([CH:22]=[O:23])[CH2:20][CH2:21]1)([CH3:12])([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 11701224tert-butyl N-{[1-(hydroxymethyl)cyclopropyl]methyl}carbamate

Product 1

HCID 45091929tert-butyl N-[(1-formylcyclopropyl)methyl]carbamateYield 27.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

Under an argon atmosphere oxalyl chloride (1.17 mL, 13.8 mmol) was dissolved in DCM (30 mL) and cooled to −70 C. DMSO (1.95 mL, 27.6 mmol) in DCM (2.5 mL) was added over 5 min and stirred for 10 min. (1-Hydroxymethyl-cyclopropylmethyl)-carbamic acid tert-butyl ester (2.6 g, 12 mmol) in DCM (8.5 mL) was added at −70 C over 5 min and the mixture was stirred for 30 min. Et3N (6.4 mL, 45.6 mmol) was added over 5 min and the temperature was allowed to reach RT over 1 h. H2O was added and the aqueous phase was extracted with DCM (×2). The combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica using heptane:EtOAc 1:15 as eluent to afford (1-Formyl-cyclopropylmethyl)-carbamic acid tert-butyl ester (0.65 g) as an oil.

Workup

  1. temperaturecooled to −70 C
  2. additionwas added at −70 C over 5 min
  3. waitto reach RT over 1 h
  4. extractionthe aqueous phase was extracted with DCM (×2)
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromatography on silica

Sources & evidence

ORD record
ord-b33a62f90cdb4f26bc816a64bdd51e0e
Source dataset
uspto-grants-2015_02
Patent number
US08952162B2

Reaction notes

Loading…