Cesium fluoride → (r)-3-(2,6-Dimethyl-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenoxy)propane-1,2-diol

HRID 1177569Notes

Reaction equation

[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[S:9][C:10]3[C:15]([N:16]=2)=[CH:14][CH:13]=[C:12]([C:17]2([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH2:19][CH2:18]2)[N:11]=3)[CH:5]=[C:4]([CH3:26])[C:3]=1[OH:27].[F-].[Cs+].[CH2:30]1[O:32][C@@H:31]1[CH2:33][OH:34]>CN(C=O)C>[CH3:26][C:4]1[CH:5]=[C:6]([C:8]2[S:9][C:10]3[C:15]([N:16]=2)=[CH:14][CH:13]=[C:12]([C:17]2([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH2:18][CH2:19]2)[N:11]=3)[CH:7]=[C:2]([CH3:1])[C:3]=1[O:27][CH2:30][C@H:31]([OH:32])[CH2:33][OH:34]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 2,6-dimethyl-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenol (35.1 mg, 94 μmol) and cesium fluoride (0.72 mg, 4.7 μmol) in anhydrous DMF (0.5 mL) was stirred at 25° C. for 1 h. (R)-(+)-glycidol (98% ee) (6.6 μl, 99 μmol) was then added, and the resulting mixture was heated under argon at 80° C. for 2 d. Additional (R)-(+)-glycidol (6.56 μl, 98.9 μmol) was then added, and the reaction mixture was heated at 80° C. for 18 h. The reaction mixture was subsequently cooled to 25° C., filtered through Celite, diluted with DMSO (1.5 mL), and purified by rpHPLC (10-100% CH3CN/water+0.1% TFA) to provide (R)-3-(2,6-dimethyl-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenoxy)propane-1,2-diol as a white solid. MS (ESI) m/z: Calculated: 446.2; Observed: 447.0 (M++1).

Workup

additionwas then added
temperaturethe reaction mixture was heated at 80° C. for 18 h
temperatureThe reaction mixture was subsequently cooled to 25° C.
filtrationfiltered through Celite
additiondiluted with DMSO (1.5 mL)
custompurified by rpHPLC (10-100% CH3CN/water+0.1% TFA)

Sources & evidence

ORD record: ord-d44b4628d6b84d7e87068e4d9a3084ec
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07842685B2

Reaction notes

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