1,2-Dimethoxyethane → Methyl 3-(2-hydroxypropan-2-yl)-1-(thiophen-3-yl)-1H-indazole-6-carboxylate

HRID 1047638Notes

Reaction equation

HRID 1047638 reaction equation
[CH2:1]=[C:2]([C:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13]([O:15][CH3:16])=[O:14])=[CH:10][CH:11]=2)[N:6]([C:17]2[CH:21]=[CH:20][S:19][CH:18]=2)[N:5]=1)[CH3:3].[BH4-].C([N+](CC)(CC)CC)C.C(COC)[O:33]C>CO.C1C=CC(C2C3=NC(C=C3)=C(C3C=CC=CC=3)C3[N-]C(=CC=3)C(C3C=CC=CC=3)=C3C=CC(=N3)C(C3C=CC=CC=3)=C3[N-]C=2C=C3)=CC=1.[Co+2]>[OH:33][C:2]([C:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13]([O:15][CH3:16])=[O:14])=[CH:10][CH:11]=2)[N:6]([C:17]2[CH:21]=[CH:20][S:19][CH:18]=2)[N:5]=1)([CH3:3])[CH3:1]

Participants

6

Reactant 3

HCID 80711,2-DimethoxyethaneHCID 28251Tetraethylammonium tetrahydroborateHCID 66661623Methyl 3-(prop-1-en-2-yl)-1-(thiophen-3-yl)-1H-indazole-6-carboxylate

Product 1

HCID 66661520Methyl 3-(2-hydroxypropan-2-yl)-1-(thiophen-3-yl)-1H-indazole-6-carboxylateYield 80%

Reagents, catalysts & solvents 2

HCID 518893meso-Tetraphenylporphine-Co(II)CatalystHCID 887MethanolSolvent

Procedure

Methyl 3-(prop-1-en-2-yl)-1-(thiophen-3-yl)-1H-indazole-6-carboxylate (1.0763 g, 3.61 mmol) was dissolved in dimethoxyethane (90 ml)/MeOH (90 ml) at 25° C. Cobalt(II) meso-tetraphenylporphine (25.6 mg, 0.038 mmol) and tetraethylammonium borohydride (1.316 g, 9.07 mmol) were added sequentially. The reaction mixture was allowed to stir for 1.25 h. The reaction was stopped, quenched by addition of saturated aqueous ammonium chloride (100 mL), and the mixture extracted with ethyl acetate (3×80 mL). The combined organic phases were washed with saturated aqueous sodium chloride (1×80 mL), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure. The crude product was purified by flash chromatography (RediSep SiO2, 330 g column) on a CombiFlash Rf purification system eluting with ethyl acetate-hexanes (0-45%). The title compound (912.2 mg, 2.88 mmol, 80% yield) was recovered as an orange solid. LC-MS: [M+1]=317.1.

Workup

  1. customquenched by addition of saturated aqueous ammonium chloride (100 mL)
  2. extractionthe mixture extracted with ethyl acetate (3×80 mL)
  3. washThe combined organic phases were washed with saturated aqueous sodium chloride (1×80 mL)
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. customthe solvent evaporated under reduced pressure
  7. customThe crude product was purified by flash chromatography (RediSep SiO2, 330 g column) on a CombiFlash Rf purification system
  8. washeluting with ethyl acetate-hexanes (0-45%)

Sources & evidence

ORD record
ord-18cb3265a838422c81948ecfad00141c
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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