Water → Methyl 3-methyl-1H-indole-6-carboxylate

HRID 1158385Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([C:9]([CH:14]=O)=[CH:10][NH:11]2)=[CH:7][CH:6]=1)=[O:4].C1(C)C=CC(S(O)(=O)=O)=CC=1.C([BH3-])#N.[Na+].O>CN(C)C=O.S1(CCCC1)(=O)=O>[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([C:9]([CH3:14])=[CH:10][NH:11]2)=[CH:7][CH:6]=1)=[O:4]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 3-formyl-1H-indole-6-carboxylic acid methyl ester (5 g, 24.6 mmol), p-toluene-sulfonic acid (704 mg, 3.7 mmol) and p-toluenesulfonylhydrazide (5.49 g, 29.5 mmol) in a mixture of dimethylformamide (50 mL) and sulfolane (25 mL) is heated at 100° C. for 15 min. Then cooled to RT, before the addition of sodium cyanoborohydride (6.2 g, 98.4 mmol, 2 g portions after 10 min intervals). The resulting mixture is heated at 100° C. for 2 h, cooled to RT and poured into a mixture of ice and water (250 mL) leading to a white precipitate. Water (500 mL) is added, and the mixture is stirred for 30 min before filtration. The off-white solid is washed with warm water. Toluene is added and removed by rotary evaporation to afford the title compound as a yellow solid. TLC, Rf (hexane/AcOEt 4:1)=0.3. MS (LC-MS): [M+H]+=188.1. tR (HPLC, Macherey-Nagel Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mL/min): 5.13 min.

Workup

temperatureThe resulting mixture is heated at 100° C. for 2 h
temperaturecooled to RT
washThe off-white solid is washed with warm water
additionToluene is added
customremoved by rotary evaporation

Sources & evidence

ORD record: ord-db66c2cba08d420c84ec73a40f7af56e
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07807709B2

Reaction notes

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