1,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)- → HCID 58384781, compound

HRID 1945357Notes

Reaction equation

HRID 1945357 reaction equation
[NH2:1][C:2]1[C:3]([CH3:11])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].[C:12]([N:19]1[CH2:26][CH2:25][CH2:24][C@H:20]1[C:21](O)=[O:22])([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]>ClCCl>[C:15]([O:14][C:12]([N:19]1[CH2:26][CH2:25][CH2:24][C@H:20]1[C:21]([NH:1][C:2]1[C:3]([CH3:11])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6])=[O:22])=[O:13])([CH3:18])([CH3:17])[CH3:16]

Participants

4

Reactant 2

HCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 27336993-Amino-2-methylbenzoic acid

Product 1

HCID 58384781HCID 58384781, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-(3-Dimethylaminopropyl)-N-ethylcarbodimide HCl salt (3.1 g, 16.6 mmol) was added to a suspension of 3-amino-2-methylbenzoic acid (2.5 g, 16.6 mmol) and N-Boc-L-proline (3.5 g, 16.6 mmol) in dichloromethane (40 mL). The reaction mixture was stirred under nitrogen for 18 h, diluted with solvent (1 vol) and washed with 1N HCl, brine, and dried (MgSO4). Concentration gave a foam with was applied to a 40 M Biotage SiO2 column, and eluted by gradient 20%-60% B (1000 mL); A=1% acetic acid/hexanes; B=1% acetic acid/ethyl acetate to give J.36 (S)-3-(1-(tert-butoxycarbonyl)pyrrolidine-2-carboxamido)-2-methylbenzoic acid 2.6 g (45%). 1H NMR (300 MHz, DMSO-d6) δ: 12.5 (br. s, 1H), 9.52/9.46 (s, 1H), 7.57 (d, J=7.3 Hz, 1H), 7.44-7.40 (m, 1H), 7.29-7.24 (m, 1H), 4.32-4.28 (m, 1H), 3.47-3.48 (m, 1H), 3.34-3.29 (m, 1H), 2.33 (s, 3H), 1.93-1.80 (m, 4H), 1.41/1.36 (s, 9H). LC (Cond.-J1): 1.55 min; LCMS: Anal. Calcd. for [M+H]+ C18H25N2O5: 349.18; found 349.33.

Workup

  1. additiondiluted with solvent (1 vol)
  2. washwashed with 1N HCl, brine
  3. dry with materialdried (MgSO4)
  4. concentrationConcentration
  5. customgave a foam
  6. washeluted by gradient 20%-60% B (1000 mL)

Sources & evidence

ORD record
ord-30b656f5400e4cf8adc0fea71956ddc9
Source dataset
uspto-grants-2013_03
Patent number
US08394968B2

Reaction notes

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