Methyl 2,3-dihydro-2-oxo-1H-indole-5-carboxylate → 5-(Hydroxymethyl)-1,3-Dihydro-2H-Indol-2-One
Reaction equation
[O:1]=[C:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:11](OC)=[O:12])[CH:8]=2)[NH:3]1.O1CCCC1.C(O)C.[BH4-].[Li+]>C(O)C>[OH:12][CH2:11][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[NH:3][C:2](=[O:1])[CH2:10]2Participants
Procedure
To an ice-cooled mixture of methyl 2-oxoindoline-5-carboxylate (0.5 gram, 2.6 mmol) in a tetrahydrofuran/ethanol mixture (15:0.3 mL) was added lithium borohydride (115 mg, 5.2 mmol) in one portion. After 30 min, another portion of lithium borohydride (100 mg, 4.5 mmol) was added and the reaction solution was stirred for 4 h at room temperature. A third portion of lithium borohydride (200 mg, 9.2 mmol) and ethanol (0.3 mL) were added and the reaction solution was stirred for 14 h at room temperature. The reaction was quenched with water (10 mL) and an aqueous saturated ammonium chloride solution (30 mL) and extracted with ethyl acetate. The combined organic phases were dried (Na2SO4) and evaporated in vacuo. The crude product was purified on a silica gel column using methylene chloride/methanol, (10:1) as the eluent to give 140 mg (33% yield) of the title compound: 1H NMR (DMSO-d6, 300 MHz) δ 10.3 (br s, 1 H), 7.14 (s, 1 H), 7.09 (d, J=8 Hz, 1 H), 6.74 (d, J=8 Hz, 1 H), 5.03 (t, J=6 Hz, 1 H), 4.41 (7, J=6 Hz, 2 H), 3.44 (s, 2 H).
Workup
- stirringthe reaction solution was stirred for 14 h at room temperature
- customThe reaction was quenched with water (10 mL)
- extractionan aqueous saturated ammonium chloride solution (30 mL) and extracted with ethyl acetate
- dry with materialThe combined organic phases were dried (Na2SO4)
- customevaporated in vacuo
- customThe crude product was purified on a silica gel column
Sources & evidence
- ORD record
- ord-25fe43d381ba4a90a3169ccf9b10662c
- Source dataset
- uspto-grants-2008_07
- Patent number
- US07399780B2
Reaction notes
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