Hydrochloric Acid → methyl (2S,4R)-4-benzamidopyrrolidine-2-carboxylate hydrochloride

HRID 1423861Notes

Reaction equation

HRID 1423861 reaction equation
[ClH:1].C([O:4][CH2:5][CH3:6])C.[NH2:7][C@H:8]1[CH2:12][N:11](C(OCC2C=CC=CC=2)=O)[C@H:10]([C:23]([O:25][CH3:26])=[O:24])[CH2:9]1>CO>[ClH:1].[C:5]([NH:7][C@H:8]1[CH2:12][NH:11][C@H:10]([C:23]([O:25][CH3:26])=[O:24])[CH2:9]1)(=[O:4])[C:6]1[CH:23]=[CH:10][CH:9]=[CH:8][CH:12]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 179988221-benzyl 2-methyl (2S,4R)-4-aminopyrrolidine-1,2-dicarboxylate

Product 1

HCID 25001497methyl (2S,4R)-4-benzamidopyrrolidine-2-carboxylate hydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
57 °C

Procedure

To the above methanol concentrate of (2S,4R)-1-benzyl 2-methyl 4-benzamidopyrrolidine-1,2-dicarboxylate, were added a slurry of 10% Pd/C (dry, 4.1 g) in methanol (100 mL) and cyclohexene (80 mL). The mixture was heated at reflux (57° C.) for 7 h. before being cooled to 20-25° C. Palladium catalyst was filtered off through a pad of Celite, and washed with methanol. The filtrate was concentrated, and cyclohexene was removed as a methanol azetrope. To the final methanol solution was added 1 N hydrogen chloride in diethyl ether (110 mL, 0.11 mol) while the temperature was maintained at 20-25° C. The resulting slurry was cooled to 10-15° C. over 20 min. The solid product was filtered and washed with toluene. The wet solid was dried at 60° C. under vacuum to give 22.4 g of (2S,4R)-methyl 4-benzamidopyrrolidine-2-carboxylate hydrochloride as white solid (81.7% overall yield from 1-benzyl 2-methyl (2S,4R)-4-aminopyrrolidine-1,2-dicarboxylate). 1H NMR (CDCl3, δ, ppm): 9.99 (bs, 2H), 8.95 (d, J=6.6 Hz, 1H), 7.97-7.94 (m, 2H), 7.58-7.45 (m, 3H), 4.71 (t, J=8.7 Hz, 1H), 4.68-4.61 (m 1H), 3.78 (s, 3H), 3.58 (dd, J=11.9, 6.6 Hz, 1H), 3.32 (dd, J=11.9, 4.2 Hz, 1H), 2.41 (d, J=8.6 Hz, 1H), 2.39 (d, J=8.6 Hz, 1H).

Workup

  1. concentrationTo the above methanol concentrate of (2S,4R)-1-benzyl 2-methyl 4-benzamidopyrrolidine-1,2-dicarboxylate
  2. additionwere added a slurry of 10% Pd/C (dry, 4.1 g) in methanol (100 mL) and cyclohexene (80 mL)
  3. temperatureThe mixture was heated
  4. temperaturebefore being cooled to 20-25° C
  5. filtrationPalladium catalyst was filtered off through a pad of Celite
  6. washwashed with methanol
  7. concentrationThe filtrate was concentrated
  8. customcyclohexene was removed as a methanol azetrope
  9. temperaturewas maintained at 20-25° C
  10. temperatureThe resulting slurry was cooled to 10-15° C. over 20 min
  11. filtrationThe solid product was filtered
  12. washwashed with toluene
  13. customThe wet solid was dried at 60° C. under vacuum
  14. customto give

Sources & evidence

ORD record
ord-e4f99611f3664cd5bd1e88b87a6248bd
Source dataset
uspto-grants-2015_01
Patent number
US08927590B2

Reaction notes

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