Dimethylformamide → 3-(2-formyl-4,5,6,7-tetrahydro-1H-indol-3-yl)propionic acid

HRID 1860899Notes

Reaction equation

CN(C)[CH:3]=[O:4].P(Cl)(Cl)(Cl)=O.[NH:11]1[C:19]2[CH2:18][CH2:17][CH2:16][CH2:15][C:14]=2[C:13]([CH2:20][CH2:21][C:22]([OH:24])=[O:23])=[CH:12]1.[OH-].[Na+]>O.ClCCl>[CH:3]([C:12]1[NH:11][C:19]2[CH2:18][CH2:17][CH2:16][CH2:15][C:14]=2[C:13]=1[CH2:20][CH2:21][C:22]([OH:24])=[O:23])=[O:4]

Participants

Conditions

Temperature: -9 °C

Procedure

A mixture of 24 g of dimethylformamide and 300 mL of dichloromethane was cooled to −9° C. Phosphorus oxychloride (50 g) was rapidly added via an addition funnel. 3-(4,5,6,7-tetrahydro-1H-indol-3-yl)-propionic acid (54.9 g) was added in portions with vigorous stirring. The mixture was warmed to room temperature and then refluxed for 10 minutes. It was then cooled to 5° C. and diluted with 300 mL of water. The pH was adjusted to 10 using 10N sodium hydroxide. The layers were separated. The aqueous layer was cooled to 10° C. and the pH adjusted to 2-3 with about 130 mL of 10 N hydrochloric acid. The oil which formed solidified and was collected by vacuum filtration, washed three times with water and dried under vacuum at 50° C. to give 52.8 g (93% yield) of 3-(2-formyl-4,5,6,7-tetrahydro-1H-indol-3-yl)-propionic acid as a dark brown solid.

Workup

temperatureThe mixture was warmed to room temperature
temperaturerefluxed for 10 minutes
temperatureIt was then cooled to 5° C.
customThe layers were separated
temperatureThe aqueous layer was cooled to 10° C.
customThe oil which formed
filtrationwas collected by vacuum filtration
washwashed three times with water
customdried under vacuum at 50° C.

Sources & evidence

ORD record: ord-93676ad8e44044849d842fe1933fabb6
Source dataset: uspto-grants-2003_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06531502B1

Reaction notes

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