Ethyl Acetate → 6-Chloro-5-hydroxy-1H-indole-2-carboxylic acid ethyl ester

HRID 19880Notes

Reaction equation

HRID 19880 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15]C)=[C:10]([Cl:17])[CH:9]=2)=[O:5])[CH3:2].B(Br)(Br)Br.C(OCC)(=O)C>ClCCl>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([OH:15])=[C:10]([Cl:17])[CH:9]=2)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 25134Boron tribromideHCID 12200732ethyl 6-chloro-5-methoxy-1H-indole-2-carboxylate

Product 1

HCID 670179146-Chloro-5-hydroxy-1H-indole-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a cooled (−78° C.) solution of 6-chloro-5-methoxy-1H-indole-2-carboxylic acid ethyl ester (example 39, step 1, 930 mg, 1.0 eq.) in dichloromethane (20 mL), was slowly added a solution of boron tribromide 1M in dichloromethane (7.33 mL, 2.0 eq.). The mixture was stirred at room temperature for 1 h, partitionned between ethyl acetate and ice water. The aqueous layer was extracted with ethyl acetate and the combined organic fractions were washed with 10% sodium bicarbonate solution and brine, dried over sodium sulfate, filtered, evaporated to dryness and purified on silica gel, eluting with a 4:1 to 3:1 gradient of cyclohexane/ethyl acetate, to yield 655 mg (74%) from the desired product as light brown solid. MS (m/e): 239.2 (M+, 35%).

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate
  2. washthe combined organic fractions were washed with 10% sodium bicarbonate solution and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness
  6. custompurified on silica gel
  7. washeluting with a 4:1 to 3:1 gradient of cyclohexane/ethyl acetate

Sources & evidence

ORD record
ord-fdf759f4776c41dda4e3debc9b32df59
Source dataset
uspto-grants-2010_06
Patent number
US07745479B2

Reaction notes

Loading…