4-Chlorobenzyl alcohol → HCID 66617965, compound

HRID 222179Notes

Reaction equation

[OH-].[K+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][OH:11])=[CH:6][CH:5]=1.Cl[C:13]1[N:18]=[CH:17][NH:16][C:15]2=[N:19][CH:20]=[CH:21][C:14]=12>O>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][O:11][C:13]2[C:14]3[CH:21]=[CH:20][NH:19][C:15]=3[N:16]=[CH:17][N:18]=2)=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a 0.375 M solution of aqueous potassium hydroxide (26.2 mL, 9.83 mmol) was added (4-chlorophenyl)methanol (464 mg, 3.26 mmol) and the mixture was heated to 80° C. for 30 min. Then 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (500 mg, 3.26 mmol) was added and the mixture was refluxed at 130° C. After 6 h, additional (4-chlorophenyl)methanol (100. g, 0.701 mmol) was added and the solution was heated to 115° C. overnight. The reaction was cooled to rt and diluted with water. The solution was then extracted with EtOAc (2×) and DCM (2×). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting crude oil was purified by silica gel chromatography eluting with a gradient of 5 to 30% EtOAc in DCM to afford the product as a white solid (210 mg, 25%). LC/MS: Rt=1.72 min, ES+ 260. (FA standard).

Workup

temperaturethe mixture was refluxed at 130° C
temperaturethe solution was heated to 115° C. overnight
temperatureThe reaction was cooled to rt
extractionThe solution was then extracted with EtOAc (2×) and DCM (2×)
dry with materialThe combined organic layers were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe resulting crude oil was purified by silica gel chromatography
washeluting with a gradient of 5 to 30% EtOAc in DCM

Sources & evidence

ORD record: ord-5900be5def794c7fa82ce002fa971126
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08207177B2

Reaction notes

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