Lithium Hydroxide → 1-((S)-2-Benzyloxycarbonylaminopropyl)-1H-furo[2,3-g]indazole-7-carboxylic acid

HRID 1453894Notes

Reaction equation

HRID 1453894 reaction equation
C([O:8][C:9]([C:11]1[O:36][C:14]2=[CH:15][CH:16]=[C:17]3[C:21]([N:20]([CH2:22][C@@H:23]([NH:25][C:26]([O:28][CH2:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:27])[CH3:24])[N:19]=[CH:18]3)=[C:13]2[CH:12]=1)=[O:10])C1C=CC=CC=1.[OH-].[Li+]>C(O)C.O>[CH2:29]([O:28][C:26]([NH:25][C@@H:23]([CH3:24])[CH2:22][N:20]1[C:21]2[C:17](=[CH:16][CH:15]=[C:14]3[O:36][C:11]([C:9]([OH:10])=[O:8])=[CH:12][C:13]3=2)[CH:18]=[N:19]1)=[O:27])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 688563631-((S)-2-Benzyloxycarbonylaminopropyl)-1H-furo[2,3-g]indazole-7-carboxylic acid benzyl ester

Product 1

HCID 688554451-((S)-2-Benzyloxycarbonylaminopropyl)-1H-furo[2,3-g]indazole-7-carboxylic acidYield 98.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of the product of Step A, Example 2 (0.15 g, 0.31 mmol) in ethanol (10 mL) was added lithium hydroxide (0.026 g, 0.62 mmol) in water (1 mL) and stirred at room temperature for 16 h. The reaction mixture was evaporated to a residue and a saturated aqueous solution of ammonium chloride (20 mL) was added followed by the addition of phosphoric acid (1 M) until the solution was neutral. The mixture was extracted with ethyl acetate (3×50 mL) and the combined extracts were washed with brine (30 mL), dried and evaporated. The residue was purified by chromatography (silica, dichloromethane, 5% methanol in dichloromethane, 10% methanol in dichloromethane) to give an oil (0.12 g, 98%): MS (ES) m/z 394 (M+); 1H NMR (CD3OD) δ 7.91 (s, 1H), 7.81 (s, 1H), 7.58 (d, 1H, J=8.8 Hz), 7.25 (d, 1H, J=8.8 Hz), 7.14-7.02 (m, 5H), 4.81 (s, 2H), 4.49-4.42 (m, 2H), 4.17 (m, 1H), 1.18 (d, 3H, J=6.8 Hz).

Workup

  1. customThe reaction mixture was evaporated to a residue
  2. additiona saturated aqueous solution of ammonium chloride (20 mL) was added
  3. additionfollowed by the addition of phosphoric acid (1 M) until the solution
  4. extractionThe mixture was extracted with ethyl acetate (3×50 mL)
  5. washthe combined extracts were washed with brine (30 mL)
  6. customdried
  7. customevaporated
  8. customThe residue was purified by chromatography (silica, dichloromethane, 5% methanol in dichloromethane, 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-791af580fca44d788c43c0877a180c75
Source dataset
uspto-grants-2009_01
Patent number
US07476687B2

Reaction notes

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