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

HRID 2111942Notes

Reaction equation

HRID 2111942 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., and then neutralized with 1M HCl (˜650 mL) that was added at such a rate that the temperature did not exceed 5° C. On addition, the mixture was diluted with H2O (1 L) and stirred while warming to ambient temperature. The resultant 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. additionwas added at such a rate that the temperature
  3. customdid not exceed 5° C
  4. additionOn addition
  5. temperaturewhile warming to ambient temperature
  6. customThe resultant precipitates
  7. filtrationwere collected by filtration
  8. washrinsed with H2O
  9. customdried

Sources & evidence

ORD record
ord-89d3fc15eaec4b70a39fba76ff452690
Source dataset
uspto-grants-2009_04
Patent number
US07521441B2

Reaction notes

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