Sodium Chloride → 4-[(1R,2R)-2-benzyloxy-1-methyl-propoxy]-2-chloro-5-(trifluoromethyl)pyrimidine

HRID 2403561Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[CH2:13]([O:20][C@H:21]([CH3:25])[C@H:22]([OH:24])[CH3:23])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[H-].[Na+].[Cl-].[Na+]>C(OCC)C.C(#N)C>[CH2:13]([O:20][C@H:21]([CH3:25])[C@@H:22]([CH3:23])[O:24][C:6]1[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

Conditions

Temperature: 15 °C

Procedure

A solution of 5.00 g (23.0 mmol) of 2,4-dichloro-5-trifluoromethylpyrimidine and 5.40 g (30.0 mmol) of (2R,3R)-3-benzyloxybutan-2-ol in 60 ml of diethyl ether and 65 ml of acetonitrile were admixed at 0° C. with 1.21 g (27.7 mmol) of sodium hydride (55% strength), divided into 3 portions, and then stirred for 90 minutes at 15° C. The mixture was admixed with dilute sodium chloride solution and extracted (3×) with ethyl acetate. The combined organic phases were dried (Na2SO4), filtered and concentrated by evaporation. The resulting residue was purified chromatographically (hexane/ethyl acetate 95:5). This gave 1.60 g (4.4 mmol; yield: 19%) of the product.

Workup

extractionextracted (3×) with ethyl acetate
dry with materialThe combined organic phases were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated by evaporation
customThe resulting residue was purified chromatographically (hexane/ethyl acetate 95:5)

Sources & evidence

ORD record: ord-e462f77f28b74b0c8056b139958fa0ba
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08802686B2

Reaction notes

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