Dimethyl Sulfoxide → 4-Methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-4,5-dihydro-1,3-oxazole-4-carbaldehyde

HRID 251457Notes

Reaction equation

C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][C:12]1([CH2:33][OH:34])[CH2:16][O:15][C:14]([C:17]2[CH:18]=[N:19][C:20]([O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:31][CH2:30][CH2:29][CH:28]3[CH3:32])=[CH:21][CH:22]=2)=[N:13]1.C(N(CC)CC)C>ClCCl.O>[CH3:11][C:12]1([CH:33]=[O:34])[CH2:16][O:15][C:14]([C:17]2[CH:18]=[N:19][C:20]([O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:31][CH2:30][CH2:29][CH:28]3[CH3:32])=[CH:21][CH:22]=2)=[N:13]1

Participants

Conditions

Temperature: 22 °C

Procedure

A solution of oxalyl chloride (0.38 ml, 4.32 mmol) in dichloromethane (30 ml) is cooled to −78° C. and is treated slowly with dimethylsulfoxide (0.51 ml, 7.2 mmol). After 20 min at −78° C., a solution of (4-methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-4,5-dihydro-1,3-oxazol-4-yl)methanol ax56 (1.2 g, 80% purity, ca. 3.0 mmol) in dichloromethane (10 ml) is added dropwise over 10 min. After 60 min at −78° C., triethylamine (2.5 ml, 18 mmol) is added and the mixture is allowed to warm to 22° C. Water is then added and after vigorous stirring, the organic layer is separated and the aqueous phase extracted twice with dichloromethane. The combined organic layers are washed with brine, dried over sodium sulfate and concentrated in vacuo to yield 1.2 g of ca. 80% pure 4-methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-4,5-dihydro-1,3-oxazole-4-carbaldehyde ax57.

Workup

waitAfter 60 min at −78° C.
customafter vigorous stirring, the organic layer is separated
extractionthe aqueous phase extracted twice with dichloromethane
washThe combined organic layers are washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-5a1f41b9016c49e5b9021ce7dd8e5c69
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07863450B2

Reaction notes

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