Hydrochloric Acid → (2S,4R)-4-benzamido-1-(2-((tert-butoxycarbonyl)amino)acetyl)pyrrolidine-2-carboxylic acid

HRID 1423857Notes

Reaction equation

HRID 1423857 reaction equation
[C:1]([NH:9][C@H:10]1[CH2:14][N:13]([C:15](=[O:25])[CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C@H:12]([C:26]([O:28]C)=[O:27])[CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.Cl>>[C:1]([NH:9][C@H:10]1[CH2:14][N:13]([C:15](=[O:25])[CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:22])[CH3:23])=[O:19])[C@H:12]([C:26]([OH:28])=[O:27])[CH2:11]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 25001500Methyl (2S,4R)-4-benzamido-1-((tert-butoxycarbonyl)glycyl)pyrrolidine-2-carboxylate

Product 1

HCID 16738323(2S,4R)-4-benzamido-1-(2-((tert-butoxycarbonyl)amino)acetyl)pyrrolidine-2-carboxylic acidYield 100.1%

Conditions

Temperature
-2 °C

Procedure

To a solution of (2S,4R)-methyl 4-benzamido-1-(2-(tert-butoxycarbonyl-amino)acetyl)pyrrolidine-2-carboxylate (23.33 g, 0.0575 mol) in methanol (450 mL) NaOH (0.2875 mol, 144 mL of 2N aqueous solution) was added at −1 to 1° C. over 15 min. The mixture was stirred at −5 to 1° C. for 2.5 h. HCl (0.2875 mol, 144 mL of 2N aqueous solution) was added at −3 to 1° C. over 25 min. MeOH was distilled off in vacuum. 500 mL of EtOAc were added. Aqueous phase was saturated with NaCl. Phases were separated. Aqueous phase was extracted with 2×250 mL of EtOAc. Combined EtOAc solution was dried over MgSO4, and concentrated to afford 22.54 g of the title product as a white foamy solid (contains 6.6 wt % EtOAc; 94% yield adjusted to residual EtOAc). 1H NMR (CD3OD, δ, ppm): 7.87-7.79 (m, 2H), 7.58-7.42 (m, 3H), 4.81-4.7 (m 1H), 4.69-4.56 (m, 1H), 4.05-3.72 (m, 3H), 3.67-3.49 (m, 1H), 2.64-2.28 (m, 2H), 1.43 (s, 9H). MS (m/z, positive ESI) for M+H: 392; for M+Na: 414.

Workup

  1. distillationMeOH was distilled off in vacuum
  2. addition500 mL of EtOAc were added
  3. customPhases were separated
  4. extractionAqueous phase was extracted with 2×250 mL of EtOAc
  5. dry with materialCombined EtOAc solution was dried over MgSO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-00bb13e0d2f142ae83adae63b205607c
Source dataset
uspto-grants-2015_01
Patent number
US08927590B2

Reaction notes

Loading…