Acetic Acid → Methyl 6-cyclopropyl-2-(methylsulfonyl)pyrimidine-4-carboxylate

HRID 1748192Notes

Reaction equation

[CH:1]1([C:4]2[N:9]=[C:8]([S:10]([CH3:13])(=[O:12])=[O:11])[N:7]=[C:6]([C:14]([OH:16])=[O:15])[CH:5]=2)[CH2:3][CH2:2]1.[CH3:17][Si](C=[N+]=[N-])(C)C.C(O)(=O)C>ClCCl.CO>[CH:1]1([C:4]2[N:9]=[C:8]([S:10]([CH3:13])(=[O:11])=[O:12])[N:7]=[C:6]([C:14]([O:16][CH3:17])=[O:15])[CH:5]=2)[CH2:2][CH2:3]1

Participants

Conditions

Temperature: 0 °C

Procedure

A suspension of 6-cyclopropyl-2-(methylsulfonyl)pyrimidine-4-carboxylic acid (200 mg, 0.82 mmol) in dichloromethane (2 mL) and methanol (0.5 mL) was cooled to 0° C. Trimethylsilyl diazomethane (2.0 M in diethyl ether, 1.0 mL, 2.0 mmol) was added dropwise as not to increase the internal temperature of the reaction. Upon complete addition the suspension became a yellow colored solution that was allowed to warm to RT and maintained for 1 h at that temperature. At this time, acetic acid was added dropwise until the mixture was colorless (c.a. 2 drops, 12 M) and the resulting solution was concentrated under vacuum to a residue. The resulting oily yellow solid was dissolved in sparing ice cold acetonitrile (0.5 mL) and allowed to precipitate to furnish an off white waxy solid. MS m/z 257.1 (M+1). 1H NMR (400 MHz, DMSO-d6): δ 8.22 (s, 1H), 3.81 (s, 3H), 3.28 (s, 3H), 2.40-2.36 (m, 1H), 1.20-1.15 (m, 2H), 1.12-1.06 (m, 2H).

Workup

temperatureto increase
customthe internal temperature of the reaction
additionUpon complete addition the suspension
temperatureto warm to RT
temperaturemaintained for 1 h at that temperature
concentrationthe resulting solution was concentrated under vacuum to a residue
dissolutionThe resulting oily yellow solid was dissolved in sparing ice cold acetonitrile (0.5 mL)
customto precipitate
customto furnish an off white waxy solid

Sources & evidence

ORD record: ord-0e1c5e61d30541e198986882a9fbd901
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09150568B2

Reaction notes

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