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

HRID 272291Notes

Reaction equation

HRID 272291 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

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/H20 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. filtrationThe precipitates were collected by filtration
  5. washrinsed with H2O
  6. customdried

Sources & evidence

ORD record
ord-91e8b14dc4ae4fb7a726a3eee0b86b23
Source dataset
uspto-grants-2008_11
Patent number
US07456166B2

Reaction notes

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