Dimethyl Sulfoxide → 3-(RS)-formyl-4-(SR)-phenylpyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1182160Notes

Reaction equation

HRID 1182160 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:15][C:16]([N:18]1[CH2:22][CH:21]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:20]([CH2:29][OH:30])[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].CCN(C(C)C)C(C)C>C(Cl)Cl>[C:11]([O:15][C:16]([N:18]1[CH2:22][CH:21]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:20]([CH:29]=[O:30])[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 21884252Tert-butyl 3-(hydroxymethyl)-4-phenylpyrrolidine-1-carboxylate

Product 1

HCID 724802973-(RS)-formyl-4-(SR)-phenylpyrrolidine-1-carboxylic acid tert-butyl esterYield 83.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 13.1 mL (26.25 mmol) of oxalyl chloride (2M in DCM) in 13 mL of anhydrous DCM were added 3.72 mL (52.5 mmol) of DMSO at −78° C. After 5 minutes of stirring, 3 g (10.5 mmol) of 3-(RS)-hydroxymethyl-4-(SR)-phenylpyrrolidine-1-carboxylic acid tert-butyl ester, previously dissolved in 15 mL of anhydrous DCM, were added dropwise. After 30 minutes additional agitation at −78° C., 18.5 mL (105 mmol) of DIPEA were added dropwise. An additional 30 minutes of agitation at 0° C. and the reaction mixture was quenched with 10 mL of water. 100 mL of water were again added and the solution was extracted with DCM (2×100 mL). The combined organic layers were dried over sodium sulfate, filtered and evaporated in vacuo. The crude yellow oil was purified by flash chromatography on silica gel (ethyl acetate/hexanes 0:100 to 20:80) yielding 2.42 g (83.7%) of 3-(RS)-formyl-4-(SR)-phenylpyrrolidine-1-carboxylic acid tert-butyl ester as a pale yellow oil.

Workup

  1. additionwere added dropwise
  2. waitAfter 30 minutes additional agitation at −78° C.
  3. customAn additional 30 minutes of agitation at 0° C. and the reaction mixture was quenched with 10 mL of water
  4. addition100 mL of water were again added
  5. extractionthe solution was extracted with DCM (2×100 mL)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe crude yellow oil was purified by flash chromatography on silica gel (ethyl acetate/hexanes 0:100 to 20:80)

Sources & evidence

ORD record
ord-dd34941b40814cd085346d194ecec029
Source dataset
uspto-grants-2007_10
Patent number
US07288548B2

Reaction notes

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