Carbon Dioxide → 1-Chloroisoquinoline-7-carboxylic acid

HRID 881016Notes

Reaction equation

Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]=[C:9]2[Cl:12])=[CH:4][CH:3]=1.[Li]CCCC.[C:18](=[O:20])=[O:19].[OH-].[Na+]>C1COCC1.C(OCC)C>[Cl:12][C:9]1[C:10]2[C:5](=[CH:4][CH:3]=[C:2]([C:18]([OH:20])=[O:19])[CH:11]=2)[CH:6]=[CH:7][N:8]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a suspension of 7-bromo-1-chloroisoquinoline (2.000 g, 8.247 mmoles) in THF (12 mL) and diethyl ether (12 mL) cooled down to −78° C. was added n-BuLi (3.96 mL, 9.9 mmol, 2.5M in hexanes). Stirred for five minutes and then bubbled carbon dioxide while venting with a needle for approximately one minute. The reaction mixture was warmed up to 0° C. and 15 mL of a 1N aqueous sodium hydroxide were added. The mixture was diluted with diethyl ether stirred for 18 h. The organic and aqueous layers were separated and the organics were washed with 1N aqueous sodium hydroxide and water. The aqueous fractions were combined and acidified to pH 4 with 1N aqueous hydrochloric acid. The resulting solids were collected by filtration and dried to give the title compound (1.252 g, 73%). +ESI (M+H) 208.1 1H NMR (400 MHz, DMSO-d6) d ppm 13.58 (br. s., 1H) 8.86 (m, 1H) 8.43 (d, J=5.67 Hz, 1H) 8.33 (dd, J=8.61, 1.57 Hz, 1H) 8.19 (d, J=8.41 Hz, 1H) 8.01 (dd, 1H)

Workup

temperatureThe reaction mixture was warmed up to 0° C.
stirringstirred for 18 h
customThe organic and aqueous layers were separated
washthe organics were washed with 1N aqueous sodium hydroxide and water
filtrationThe resulting solids were collected by filtration
customdried

Sources & evidence

ORD record: ord-f4392798e74d4221be94c9a2b9c6425f
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08993586B2

Reaction notes

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