Water → HCID 10457544, compound

HRID 1787963Notes

Reaction equation

HRID 1787963 reaction equation
C[O:2][C:3](=[O:34])[CH2:4][C@@H:5]([N:17]1[CH2:25][C:24]2[C:19](=[C:20]([NH:27][C:28]([CH:30]3[CH2:32][CH2:31]3)=[O:29])[CH:21]=[CH:22][C:23]=2[Cl:26])[C:18]1=[O:33])[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][CH2:15][CH3:16])[CH:7]=1.[OH-].[Na+].O>C1COCC1>[Cl:26][C:23]1[CH:22]=[CH:21][C:20]([NH:27][C:28]([CH:30]2[CH2:31][CH2:32]2)=[O:29])=[C:19]2[C:24]=1[CH2:25][N:17]([C@@H:5]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][CH2:15][CH3:16])[CH:7]=1)[CH2:4][C:3]([OH:34])=[O:2])[C:18]2=[O:33]

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 10390727HCID 10390727, compound

Product 1

HCID 10457544HCID 10457544, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3R)-3-[4-chloro-7-(cyclopropanecarbonyl-amino)-1-oxo-1,3-dihydro-isoindol-2-yl]-3-(3-ethoxy-4-methoxy-phenyl)-propionic acid methyl ester (3.0 g, 6.2 mmol) in THF (60 ml) was added NaOH (10N, 1.2 ml, 12 mmol). The mixture was stirred at room temperature overnight. To it was added water (50 ml). The mixture was extracted with EtOAc (50 ml×2). The aqueous layer was acidified by conc. HCl until pH=6. The resulted cloudy mixture was extracted with EtOAc (50 ml×2). The organice layer washed with water (30 ml×2), brine (30 ml), dried over Na2SO4, filtered and concentrated in vacuo to give (3R)-3-[4-chloro-7-(cyclopropanecarbonyl-amino)-1-oxo-1,3-dihydro-isoindol-2-yl]-3-(3-ethoxy-4-methoxy-phenyl)-propionic acid as a white solid (2.8 g, 99%): mp, 1118-120° C., 1H NMR (CDCl3) δ 0.86-0.91 (m, 2H, c-CH2), 1.05-1.11 (m, 2H, c-CH2), 145 (t, J=7.0 Hz, 3H, OCH2CH3), 1.65-1.70 (m, 1H, c-CH), 3.13 (dd, J=6, 15 Hz, 1H, CHH), 3.23 (dd, J=10, 15 Hz, 1H, CHH), 3.86 (s, 3H, OCH3), 4.00-4.11 (m, 3H, NCHH+OCH2CH3), 4.32 (d, J=18 Hz, 1H, NCHH), 5.80-5.86 (m, 1H, CHN), 6.83-6.92 (m, 3H, Ar), 7.35 (d, J=9 Hz, 1H, Ar), 8.41 (d, J=9 Hz, 1H, Ar), 10.39 (s, 1H, NHCO). 13C NMR (CDCl3): δ 8.4, 8.5, 14.7, 16.1, 36.7, 45.9, 51.8, 55.9, 64.6, 111.5, 112.4, 118.9, 119.0, 1198, 121.9, 130.1, 132.9, 136.7, 139.0, 148.7, 149.5, 168.7, 172.8, 173.8; Anal Calcd for C24H25ClN2O6+0.37H2O: C, 60.11; H, 5.41; N, 5.84. Found: C, 60.11; H, 5.25; N, 5.64, H2O, 1.40.

Workup

  1. extractionThe mixture was extracted with EtOAc (50 ml×2)
  2. extractionThe resulted cloudy mixture was extracted with EtOAc (50 ml×2)
  3. washThe organice layer washed with water (30 ml×2), brine (30 ml)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-87d8d94fcf83444bbd3e044f1f4cf88b
Source dataset
uspto-grants-2009_03
Patent number
US07511072B2

Reaction notes

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