Sodium Hydroxide → 3-(7-Acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid

HRID 1367076Notes

Reaction equation

HRID 1367076 reaction equation
C[O:2][C:3](=[O:33])[CH2:4][CH:5]([N:19]1[CH2:27][C:26]2[C:21](=[C:22]([NH:28][C:29](=[O:31])[CH3:30])[CH:23]=[CH:24][CH:25]=2)[C:20]1=[O:32])[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH:13]([F:15])[F:14])=[C:8]([O:16][CH2:17][CH3:18])[CH:7]=1.[OH-].[Na+]>C1COCC1>[C:29]([NH:28][C:22]1[CH:23]=[CH:24][CH:25]=[C:26]2[C:21]=1[C:20](=[O:32])[N:19]([CH:5]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH:13]([F:14])[F:15])=[C:8]([O:16][CH2:17][CH3:18])[CH:7]=1)[CH2:4][C:3]([OH:33])=[O:2])[CH2:27]2)(=[O:31])[CH3:30]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 102537893-(7-Acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid methyl ester

Product 1

HCID 104788263-(7-Acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acidYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To the THF solution of 3-(7-acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid methyl ester (2.5 g, 5.4 mmol) was added dropwise 10N NaOH (1 ml, 10 mmol) and was stirred at room temperature overnight. The resulted suspension was filtered and the solid was dissolved in water (20 ml). The aqueous solution was acidified to pH=4 to obtain a milky suspension. The suspension was extracted with EtOAc (50 ml×3). The organic layer was washed with water (50 ml×2), brine (30 ml), dried over Na2SO4 and concentrated to give white solid (2.3 g, 96% yield): mp 105-107° C.; 1HNMR (CDCl3): δ 1.42 (J=7.5 Hz, 3H, OCH2CH3), 2.22 (s, 3H), 3.11 (dd, J=5, 12 Hz, 1H, CH2), 3.25 (dd, J=10, 15 Hz, 1H, CH2), 4.08 (q, J=7.5 Hz, 2H, OCH2CH3), 4.12 (d, J=17.5 Hz, 1H, CH2N), 4.38 (d, J=17.5 Hz, 1H, CH2N), 5.81 (m, 1H, CHN), 6.55 (t, JH-F=75 Hz, 1H, CF2H), 6.96 (m, 3H, Ar), 7.13 (d, J=7.5 Hz, 1H, Ar), 7.45 (m, 1H, Ar), 8.43 (d, J=7.5 Hz, 1H, Ar), 10.25 (s, 1H, NHCO). 13CNMR (CDCl3): δ 14.6, 24.8, 36.7, 46.8, 51.7, 64.9, 111.8, 111.3, 115.9, 117.1, 117.3, 118.0, 118.9, 120.1, 122.8, 133.5, 136.7, 137.8, 140.1, 141.2, 150.9, 169.47, 169.49, 173.5; Anal. Calcd. for C22H22F2N2O6+0.22H2O: C, 58.41; H, 5.00; N, 6.19. Found: C, 58.06; H, 4.92; N, 5.90.

Workup

  1. filtrationThe resulted suspension was filtered
  2. dissolutionthe solid was dissolved in water (20 ml)
  3. customto obtain a milky suspension
  4. extractionThe suspension was extracted with EtOAc (50 ml×3)
  5. washThe organic layer was washed with water (50 ml×2), brine (30 ml)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-1173be803fb84c78b60096d083a1cda8
Source dataset
uspto-grants-2011_02
Patent number
US07893102B2

Reaction notes

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