Hydrochloric Acid → 6-Fluoro-5-(5-hydroxy-pent-1-ynyl)-indole-1-carboxylic acid tert-butyl ester

HRID 2212547Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13](Br)=[C:14]([F:17])[CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:19]([OH:24])[CH2:20][CH2:21][C:22]#[CH:23].O.Cl>N1CCCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:23]#[C:22][CH2:21][CH2:20][CH2:19][OH:24])=[C:14]([F:17])[CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 3.04 g (9.67 mmol) 5-Bromo-6-fluoro-indole-1-carboxylic acid tert-butyl ester, 670 mg (0.58 mmol) Pd(PPh3)4, and 111 mg (0.58 mmol) CuI in 25 ml of piperidine was heated to 60° C., treated with 1.61 ml (1.80 mmol) 4-pentyne-1-ol and stirred at 80° C. for 2 hrs. After cooling to room temperature the mixture was poured into water, acidified with 2M aqueous HCl and extracted with EtOAc. Drying of the combined organic layers with MgSO4, evaporation of the solvent, and chromatography on silica gel with CH2Cl2 gave 2.6 g (85%) of 6-Fluoro-5-(5-hydroxy-pent-1-ynyl)-indole-1-carboxylic acid tert-butyl ester as a viscous orange oil, MS: 318 (MH+).

Workup

temperatureAfter cooling to room temperature the mixture
extractionextracted with EtOAc
dry with materialDrying of the combined organic layers with MgSO4, evaporation of the solvent, and chromatography on silica gel with CH2Cl2

Sources & evidence

ORD record: ord-86eb5875a89d44688bfd9b1733c7465d
Source dataset: uspto-grants-2006_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07102007B2

Reaction notes

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