3-Amino-5-(2-oxo-pyrrolidin-1-yl)-benzoic acid → (2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-hydroxy-5-(2-oxopyrrolidin-1-yl)benzamido)propyl)-4-propoxypyrrolidine-1-carboxylate

HRID 20950

Reaction equation

HRID 20950 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:43]=[C:44](C(OC)=O)[CH:45]=1)[C:5]([NH:7][C@@H:8]([CH2:34][C:35]1[CH:40]=[C:39]([F:41])[CH:38]=[C:37]([F:42])[CH:36]=1)[C@@H:9]([C@H:18]1[CH2:22][C@@H:21]([O:23][CH2:24][CH2:25][CH3:26])[CH2:20][N:19]1[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])=[O:6].NC1C=C(C=C([N:60]2[CH2:64][CH2:63][CH2:62][C:61]2=[O:65])C=1)C(O)=O.C([O:69][C@H]1CN(C(OC(C)(C)C)=O)[C@@H](C(O)=O)C1)C=C>[Pd].CO>[Si:11]([O:10][C@H:9]([C@H:18]1[CH2:22][C@@H:21]([O:23][CH2:24][CH2:25][CH3:26])[CH2:20][N:19]1[C:27]([O:29][C:30]([CH3:33])([CH3:31])[CH3:32])=[O:28])[C@@H:8]([NH:7][C:5](=[O:6])[C:4]1[CH:3]=[C:2]([N:60]2[CH2:64][CH2:63][CH2:62][C:61]2=[O:65])[CH:45]=[C:44]([OH:69])[CH:43]=1)[CH2:34][C:35]1[CH:36]=[C:37]([F:42])[CH:38]=[C:39]([F:41])[CH:40]=1)([C:14]([CH3:16])([CH3:17])[CH3:15])([CH3:12])[CH3:13]

Participants

6

Reactant 3

HCID 222529903-Amino-5-(2-oxo-pyrrolidin-1-yl)-benzoic acidHCID 67315699(4R)-1-Boc-4-(2-propen-1-yloxy)-D-prolineHCID 67315749(2R,4R)-tert-butyl 2-((1S,2S)-2-(3-bromo-5-(methoxycarbonyl)benzamido)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylate

Product 1

HCID 59346851(2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-hydroxy-5-(2-oxopyrrolidin-1-yl)benzamido)propyl)-4-propoxypyrrolidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Step I (3): 3-Amino-5-(2-oxopyrrolidin-1-yl)benzoic acid. A suspension of 3-nitro-5-(2-oxopyrrolidin-1-yl)benzoic acid (Step I (2), 180 mg) and palladium on carbon (10 wt %, 50 mg) in MeOH (15 mL) was shaken in hydrogenator under hydrogen at 50 psi for 3 h. The mixture was filtered and concentrated in vacuo to give 140 mg of the title compound: 1H NMR (CD3OD, 500 MHz) δ ppm 2.16 (2H, m), 2.59 (2H, m), 3.89 (2H, t, J=5 Hz), 7.21 (1H, m), 7.26 (1H, m), 7.49 (1H, m). MS (ESI) (M+H)+ 221.14.

Workup

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-090dc379b36b4ed9bfd87fbca1921fa8
Source dataset
uspto-grants-2010_06
Patent number
US07745470B2

Linked notes

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