Sodium methanethiolate → (R)-4-(2-chloro-6-(methylthiomethyl)pyrimidin-4-yl)-3-methylmorpholine

HRID 1465840Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][C@H:9]2[CH3:14])[CH:5]=[C:4]([CH2:15]I)[N:3]=1.[CH3:17][S-:18].[Na+]>CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][C@H:9]2[CH3:14])[CH:5]=[C:4]([CH2:15][S:18][CH3:17])[N:3]=1

Participants

Conditions

Temperature: 25 °C

Procedure

(R)-4-(2-Chloro-6-(iodomethyl)pyrimidin-4-yl)-3-methylmorpholine (17.0 g, 48.08 mmol) was dissolved in DMF (150 ml), to this was added sodium methanethiolate (3.37 g, 48.08 mmol) and the reaction was stirred for 1 hour at 25° C. The reaction mixture was quenched with water (50 ml) and then extracted with Et2O (3×50 ml). The organic layer was dried over MgSO4, filtered and then evaporated. The residue was purified by flash chromatography on silica, eluting with a gradient of 50 to 100% EtOAc in iso-hexane. Pure fractions were evaporated to afford (R)-4-(2-chloro-6-(methylthiomethyl)pyrimidin-4-yl)-3-methylmorpholine (12.63 g, 96%); m/z: (ES+) MH+, 274.35.

Workup

customThe reaction mixture was quenched with water (50 ml)
extractionextracted with Et2O (3×50 ml)
dry with materialThe organic layer was dried over MgSO4
filtrationfiltered
customevaporated
customThe residue was purified by flash chromatography on silica
washeluting with a gradient of 50 to 100% EtOAc in iso-hexane
customPure fractions were evaporated

Sources & evidence

ORD record: ord-d894a1aabef448d8b3ec9257dd8d296c
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08999997B2

Reaction notes

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