Isopropyl Acetate → 1H-​Indole-​6-​carboxylic acid, 2-​bromo-​3-​cyclopentyl-​1-​methyl-​, 1-​methylethyl ester

HRID 1907890Notes

Reaction equation

HRID 1907890 reaction equation
[CH:1]1([C:6]2[C:14]3[C:9](=[CH:10][C:11]([C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16])=[CH:12][CH:13]=3)[N:8]([CH3:21])[CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(OC(C)C)(=O)C.[Br:29]Br>>[Br:29][C:7]1[N:8]([CH3:21])[C:9]2[C:14]([C:6]=1[CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5]1)=[CH:13][CH:12]=[C:11]([C:15]([O:17][CH:18]([CH3:19])[CH3:20])=[O:16])[CH:10]=2

Participants

4

Reactant 3

HCID 7915Isopropyl AcetateHCID 24408BromineHCID 66835544Propan-2-yl 3-cyclopentyl-1-methyl-1H-indole-6-carboxylate

Product 1

HCID 668358531H-​Indole-​6-​carboxylic acid, 2-​bromo-​3-​cyclopentyl-​1-​methyl-​, 1-​methylethyl esterYield 80%

Conditions

Temperature
-5 °C

Procedure

The mixture of isopropyl 3-cyclopentyl-1-methyl-1H-indole-6-carboxylate (84 g, 0.294 mol) and isopropyl acetate (1074 g) was cooled to between −10-0° C. Bromine (50 g, 0.312 mol) was added while the batch was maintained at −10-0° C. The resulting slurry was stirred at the same temperature for additional 30 min and quenched with a pre-cooled solution of sodium thiosulfate pentahydrate (13 g) and triethylamine (64.5 g) in water (240 g) while the temperature was maintained at 0-10° C. The mixture was heated to 40-50° C. and charged with methanol (664 g). After it was stirred at the same temperature for at least 0.5 h, the batch was cooled to 0-10° C. and stirred for another 1 hr. The precipitate was filtered, rinsed with 56 wt % methanol/water solution (322 g), and dried in vacuo (≦200 Torr) at 50-60° C. until the water content was ≦0.4% to give isopropyl 2-bromo-3-cyclopentyl-1-methyl-1H-indole-6-carboxylate as a beige solid (90-95 g, 80-85% yield).

Workup

  1. temperaturewas maintained at −10-0° C
  2. customquenched with a pre-cooled solution of sodium thiosulfate pentahydrate (13 g) and triethylamine (64.5 g) in water (240 g) while the temperature
  3. temperaturewas maintained at 0-10° C
  4. temperatureThe mixture was heated to 40-50° C.
  5. additioncharged with methanol (664 g)
  6. stirringAfter it was stirred at the same temperature for at least 0.5 h
  7. temperaturethe batch was cooled to 0-10° C.
  8. stirringstirred for another 1 hr
  9. filtrationThe precipitate was filtered
  10. washrinsed with 56 wt % methanol/water solution (322 g)
  11. dry with materialdried in vacuo (≦200 Torr) at 50-60° C. until the water content

Sources & evidence

ORD record
ord-fb04b8b3b94d4d1fb0617c173e33464d
Source dataset
uspto-grants-2013_12
Patent number
US08598183B2

Reaction notes

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