Water → Propan-2-yl 3-cyclopentyl-1-methyl-1H-indole-6-carboxylate

HRID 1907887Notes

Reaction equation

[CH:1]1([C:6]2[C:14]3[C:9](=[CH:10][C:11]([C:15](OC)=[O:16])=[CH:12][CH:13]=3)[N:8]([CH3:19])[CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:20][CH:21]([CH3:23])[O-:22].[Li+].O>CC(O)C>[CH:1]1([C:6]2[C:14]3[C:9](=[CH:10][C:11]([C:15]([O:22][CH:21]([CH3:23])[CH3:20])=[O:16])=[CH:12][CH:13]=3)[N:8]([CH3:19])[CH:7]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

Conditions

Temperature: 65 °C

Procedure

The mixture of methyl 3-cyclopentyl-1-methyl-1H-indole-6-carboxylate (50.0 g, 0.194 mol) and lithium isopropoxide (16.2 g, 95%, 0.233 mol) in 2-propanol was stirred at 65±5° C. for at least 30 min for complete trans-esterification. The batch was cooled to 40±5° C. and water (600 g) was added at a rate to maintain the batch temperature at 40±5° C. After addition, the mixture was cooled to 20-25° C. over 2±0.5 h and held at 20-25° C. for at least 1 h. The batch was filtered and rinsed with 28 wt % 2-propanol in water (186 g), and water (500 g). The wet cake was dried in vacuo (≦200 Torr) at 40-45° C. until the water content was ≦0.5% to give isopropyl 3-cyclopentyl-1-methyl-1H-indole-6-carboxylate (52.7 g, 95% yield) in 99.2 A % (240 nm).

Workup

temperatureThe batch was cooled to 40±5° C.
temperatureto maintain the batch temperature at 40±5° C
additionAfter addition
temperaturethe mixture was cooled to 20-25° C. over 2±0.5 h
waitheld at 20-25° C. for at least 1 h
filtrationThe batch was filtered
washrinsed with 28 wt % 2-propanol in water (186 g), and water (500 g)
dry with materialThe wet cake was dried in vacuo (≦200 Torr) at 40-45° C. until the water content

Sources & evidence

ORD record: ord-e9124e6e20e5438b947575858e1ce6e3
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598183B2

Reaction notes

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