Methanol → 1-tert-Butyl 2-methyl (2S,4R)-4-{[6-(benzyloxy)pyridin-2-yl]oxy}pyrrolidine-1,2-dicarboxylate

HRID 1255522Notes

Reaction equation

HRID 1255522 reaction equation
[CH2:1]([O:8][C:9]1[N:14]=[C:13]([O:15][C@H:16]2[CH2:20][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@H:18]([C:28]([OH:30])=[O:29])[CH2:17]2)[CH:12]=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.[CH3:33][Si](C=[N+]=[N-])(C)C.C(OCC)C>ClCCl>[CH2:1]([O:8][C:9]1[N:14]=[C:13]([O:15][C@H:16]2[CH2:20][N:19]([C:21]([O:23][C:24]([CH3:26])([CH3:27])[CH3:25])=[O:22])[C@H:18]([C:28]([O:30][CH3:33])=[O:29])[CH2:17]2)[CH:12]=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 3283Diethyl EtherHCID 167693TrimethylsilyldiazomethaneHCID 58158006(4R)-4-{[6-(Benzyloxy)pyridin-2-yl]oxy}-1-(tert-butoxycarbonyl)-L-proline

Product 1

HCID 581580861-tert-Butyl 2-methyl (2S,4R)-4-{[6-(benzyloxy)pyridin-2-yl]oxy}pyrrolidine-1,2-dicarboxylateYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 500 mL round bottom flask under nitrogen was charged with the product of Step 2 (7.17 g, 17.30 mmol), methanol (50 ml), and dichloromethane (50 ml). Attached an addition funnel containing trimethylsilyldiazomethane in diethyl ether (2.0M) (25.9 ml, 51.9 mmol). Cooled reaction flask in an ice bath. Added contents of addition funnel dropwise. Bubbles. HPLC/MS looks good after 0.5 hours. Quenched by dropwise addition of 2.5% potassium bisulfate. Evaporated to remove methanol. Added water. Extracted three times with ethyl acetate, dried with anhydrous magnesium sulfate, filtered and rotary evaporated filtrate. Subjected to flash column chromatography eluting with 80 hexane/20 ethyl acetate. Evaporation of fractions containing product gave the title compound as a colorless oil. (6.50 g, 15.17 mmol, 88% yield). LCMS (ES+) m/z 429.3 (M+H)+.

Workup

  1. temperatureCooled
  2. customreaction flask in an ice bath
  3. additionAdded contents of addition funnel dropwise
  4. customQuenched by dropwise addition of 2.5% potassium bisulfate
  5. customEvaporated
  6. customto remove methanol
  7. extractionExtracted three times with ethyl acetate
  8. dry with materialdried with anhydrous magnesium sulfate
  9. filtrationfiltered
  10. washeluting with 80 hexane/20 ethyl acetate
  11. customEvaporation of fractions
  12. additioncontaining product

Sources & evidence

ORD record
ord-e8842f3f5ecf44a1abc69f5cdd3e867a
Source dataset
uspto-grants-2013_06
Patent number
US08461107B2

Reaction notes

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