Dimethyl Sulfoxide → (1S,2S,5R)-2-formyl-7-methyl-3-aza-bicyclo[3.3.0]-octane-3-carboxylic acid tert.-butyl ester

HRID 425796Notes

Reaction equation

HRID 425796 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:15][C:16]([N:18]1[CH2:25][C@H:24]2[C@H:20]([CH2:21][CH:22]([CH3:26])[CH2:23]2)[C@H:19]1[CH2:27][OH:28])=[O:17])([CH3:14])([CH3:13])[CH3:12].CCN(C(C)C)C(C)C>C(Cl)Cl.O>[C:11]([O:15][C:16]([N:18]1[CH2:25][C@H:24]2[C@H:20]([CH2:21][CH:22]([CH3:26])[CH2:23]2)[C@H:19]1[CH:27]=[O:28])=[O:17])([CH3:13])([CH3:14])[CH3:12]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 66703846(1S,2S,5R)-2-hydroxymethyl-7-methyl-3-aza-bicyclo[3.3.0]-octane-3-carboxylic acid tert.-butyl ester

Product 1

HCID 86643542(1S,2S,5R)-2-formyl-7-methyl-3-aza-bicyclo[3.3.0]-octane-3-carboxylic acid tert.-butyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a cold (−60° C.) solution of oxalyl chloride (0.081 mL, 1.2 eq) in dry DCM (2.2 mL) was added dropwise a solution of DMSO (0.13 mL, 2.2 eq) in dry DCM (1.7 mL) within 4 min. After 10 min, was added dropwise (1S,2S,5R)-2-hydroxymethyl-7-methyl-3-aza-bicyclo[3.3.0]-octane-3-carboxylic acid tert.-butyl ester (206 mg) in dry DCM (1.2 mL) during 5 min. After 2 min a white suspension was formed. Stirring was continued 30 min at −55° C., then DIPEA (0.690 mL, 5 eq) (which was dried over 3A M.S.) was added during 3-4 min. The reaction mixture was allowed to come to RT, diluted with water and extracted with DCM. The combined org. extracts were washed with citric acid (5%), brine, dried over anh. MgSO4, filtered and evaporated to yield the title compound as an oil, which was used for the next step without further purification.

Workup

  1. customAfter 2 min a white suspension was formed
  2. waitwas continued 30 min at −55° C.
  3. customto come to RT
  4. extractionextracted with DCM
  5. washextracts were washed with citric acid (5%), brine
  6. dry with materialdried over anh. MgSO4
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-90a6390a916b42539bec1d8bbd43bad4
Source dataset
uspto-grants-2012_01
Patent number
US08106215B2

Reaction notes

Loading…