Water → HCID 10457544, compound

HRID 1797239Notes

Reaction equation

HRID 1797239 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 was 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, 118–120° C.; 1H NMR (CDCl3) δ 0.86–0.91 (m, 2H, c-CH2), 1.05–1.11 (m, 2H, c-CH2), 1.45 (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). 13CNMR (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+0.37 H2O: 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 was 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-36d6783a4c224aa19956c3e658fdb98d
Source dataset
uspto-grants-2006_04
Patent number
US07034052B2

Reaction notes

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