Hydrochloric Acid → HCID 10615221, compound

HRID 2292773Notes

Reaction equation

HRID 2292773 reaction equation
[Cl:1][C:2]1[N:3]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:4]2[C:9]([C:10]=1[CH2:11][C:12]([NH2:14])=[O:13])=[CH:8][C:7]([O:15]C)=[CH:6][CH:5]=2.B(Br)(Br)Br.C(Cl)Cl.Cl>C(Cl)Cl>[Cl:1][C:2]1[N:3]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:4]2[C:9]([C:10]=1[CH2:11][C:12]([NH2:14])=[O:13])=[CH:8][C:7]([OH:15])=[CH:6][CH:5]=2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 10735090HCID 10735090, compoundHCID 22277759Boron tribromide dichloromethane

Product 1

HCID 10615221HCID 10615221, compoundYield 103.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 140 mg (0.43 mmol) of 2-chloro-5-methoxy-1-(phenylmethyl)-1H-indole-3-acetamide (Example 11) in 20 mL of methylene chloride was treated with 2 mL of 1M BBr3 /CH2Cl2, stirred for 1.5 hours, stirred with aqueous HCl, the CH2Cl2 solvent separated, and washed with water, saturated NaCl solution and dried (Na2SO4). On concentrating at reduced pressure, there was obtained 140 mg of crude 2-chloro-5-hydroxy-1-(phenylmethyl)-1H-indole-3-acetamide. This material was dissolved in 15 mL of DMSO, 20 mg of 60% NaH/mineral oil added, and after 5 minutes, 0.1 mL of ethyl 4-bromobutyrate was added. The reaction mixture was heated by oil bath at 70° C. for 70 minutes. After cooling, the mixture was diluted with water, extracted with EtOAc, the EtOAc solution washed with water, saturated NaCl solution and dried (Na2SO4). After concentrating, a residue was obtained that was chromatographed on silca (eluted with CH2Cl2 →3% MeOH/CH2Cl2) to give 105 mg of 4-[[3-(2-amino-2-oxoethyl)-2-chloro-1-(phenylmethyl)-1H-indole-5-yl]oxy]butanoic acid ethyl ester. This ester (105 mg) was dissolved in 15 mL of EtOH, 1 mL of 5N NaOH added, and the solution stirred for 18 hours. The mixture was made acidic with 5N HCl, and extracted with EtOAc. The EtOAc solution was washed with saturated NaCl solution, dried (Na2 SO4) and concentrated at reduced pressure. The residue was dissolved in MeOH/CH2Cl2, the solution concentrated, to give 75 mg (80% yield) of 4-[[3-(2-amino-2-oxoethyl)-2-chloro-1-(phenylmethyl)-1H-indol-5-yl]oxy]butanoic acid, mp, 198°-200° C.

Workup

  1. customthe CH2Cl2 solvent separated
  2. washwashed with water, saturated NaCl solution
  3. dry with materialdried (Na2SO4)
  4. concentrationOn concentrating at reduced pressure

Sources & evidence

ORD record
ord-3bf0fe7d66a04283879ce32a9c3b54e9
Source dataset
uspto-grants-1997_11
Patent number
US05684034

Reaction notes

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