Hydrochloric Acid → 3-(3-Cyclopropylmethoxy-4-difluoromethoxy-phenyl)-3-(7-nitro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid

HRID 1694255Notes

Reaction equation

HRID 1694255 reaction equation
C[O:2][C:3](=[O:34])[CH2:4][CH:5]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH:26]([F:28])[F:27])=[C:21]([O:29][CH2:30][CH:31]2[CH2:33][CH2:32]2)[CH:20]=1)[N:6]1[CH2:14][C:13]2[C:8](=[C:9]([N+:15]([O-:17])=[O:16])[CH:10]=[CH:11][CH:12]=2)[C:7]1=[O:18].[OH-].[Na+].Cl>CO>[CH:31]1([CH2:30][O:29][C:21]2[CH:20]=[C:19]([CH:5]([N:6]3[CH2:14][C:13]4[C:8](=[C:9]([N+:15]([O-:17])=[O:16])[CH:10]=[CH:11][CH:12]=4)[C:7]3=[O:18])[CH2:4][C:3]([OH:34])=[O:2])[CH:24]=[CH:23][C:22]=2[O:25][CH:26]([F:28])[F:27])[CH2:33][CH2:32]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 103902253-(3-Cyclopropylmethoxy-4-difluoromethoxy-phenyl)-3-(7-nitro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid methyl ester

Product 1

HCID 103670723-(3-Cyclopropylmethoxy-4-difluoromethoxy-phenyl)-3-(7-nitro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acidYield 90%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-3-(7-nitro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid methyl ester (550 mg, 1.2 mmol) in methanol (5 ml) was added dropwise 10 N NaOH (0.23 ml, 2.3 mmol) at 0° C. The mixture was stirred at 0° C. for 1 hour. Then it was allowed to warm up to room temperature and stirred for 2 hours. 4N HCl was added until pH=5. The mixture was extracted with methylene chloride (30 ml) and 1N HCl (30 ml). The organic layer was washed with water (2×30 ml), brine (30 ml) and dried over magnesium sulfate. The solvent was removed in vacuo to give 3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-3-(7-nitro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid as a yellow solid (480 mg, 90%). 1HNMR (CDCl3): δ 0.31-0.37 (m, 2H), 0.59-0.67 (m, 2H), 1.22-1.28 (m, 1H), 3.11 (dd, J=6.5, 15 Hz, 1H), 3.33 (dd, J=9, 15 Hz, 1H), 3.78-3.87 (m, 2H), 4.18 (d, J=17.5 Hz, 1H), 4.46 (d, J=17.5 Hz, 1H), 5.83 (dd, J=6.5, 9 Hz, 1H), 6.61 (t, JH-F=75 Hz, 1H), 6.91-7.17 (m, 3H), 7.59-7.76 (m, 3H).

Workup

  1. temperatureto warm up to room temperature
  2. stirringstirred for 2 hours
  3. extractionThe mixture was extracted with methylene chloride (30 ml) and 1N HCl (30 ml)
  4. washThe organic layer was washed with water (2×30 ml), brine (30 ml)
  5. dry with materialdried over magnesium sulfate
  6. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-02522850e9dd4fbda3d4bfbd6face770
Source dataset
uspto-grants-2012_04
Patent number
US08158672B2

Reaction notes

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