Hydrochloric Acid → 1H-indole-6-carboxylic acid

HRID 2111587Notes

Reaction equation

HRID 2111587 reaction equation
Br[C:2]1[NH:3][C:4]2[C:9]([C:10]=1C1CCCCC1)=[CH:8][CH:7]=[C:6]([C:17]([O:19]C)=[O:18])[CH:5]=2.O[Li].O.Cl.C1COCC1>CO.C1COCC1.O.O>[NH:3]1[C:4]2[C:9](=[CH:8][CH:7]=[C:6]([C:17]([OH:19])=[O:18])[CH:5]=2)[CH:10]=[CH:2]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 11175076Methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 5952301H-indole-6-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
2 °C

Procedure

A solution of methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (117 g, 349 mmol) and LiOH.H2O (26.4 g, 629 mmol) in MeOH/THF/H2O (1:1:1, 1.8 L) was heated at reflux for 3 h. The reaction mixture was cooled in an ice/H2O bath to ˜2° C., neutralized with 1M HCl (˜650 mL) (added at such a rate that temperature did not exceed 5° C.), diluted with H2O (1 L) and stirred while warming to ambient temperature. The precipitates were collected by filtration rinsed with H2O and dried to yield the mono THF solvate of 1H-indole-6-carboxylic acid, 2-bromo-3-cyclohexyl- (135.5 g, 345 mmol, 99%) as a yellow solid, which was used without further purification. 1HNMR (300 MHz, CDCl3) δ 11.01 (br s, 1H), 8.77 (s, 1H), 8.07 (d, J=1.5 Hz, 1H), 7.82 (dd, J=1.5, 8.8 Hz, 1H), 7.72 (d, J=8.8 Hz, 1H), 3.84-3.74 (m, 4H), 2.89 (m, 1H), 1.98-1.72 (m, 11H), 1.50-1.24 (m, 3H). 13CNMR (75 MHz, CDCl3) δ 172.7, 135.5, 130.7, 122.3, 120.9(2), 118.8, 113.3, 111.1, 67.9(2), 37.0, 32.2(2), 27.0 (2), 26.1, 25.5(2). LCMS: m/e 320 (M−H)−, ret time 2.21 min, column A, 4 minute gradient.

Workup

  1. temperatureat reflux for 3 h
  2. additionadded at such a rate that temperature
  3. customdid not exceed 5° C.
  4. temperaturewhile warming to ambient temperature
  5. filtrationThe precipitates were collected by filtration
  6. washrinsed with H2O
  7. customdried

Sources & evidence

ORD record
ord-ae48a280bb5441e086d5ee0831f61466
Source dataset
uspto-grants-2009_04
Patent number
US07521444B2

Reaction notes

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