Sodium hydride → Cyano-(2-methylthio-pyrimidin-4-yl)-acetic acid tert-butyl ester

HRID 629484Notes

Reaction equation

[H-].[Na+].[C:3]([CH2:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])#[N:4].[H][H].Cl[C:16]1[CH:21]=[CH:20][N:19]=[C:18]([S:22][CH3:23])[N:17]=1>CS(C)=O>[C:9]([O:8][C:6](=[O:7])[CH:5]([C:3]#[N:4])[C:16]1[CH:21]=[CH:20][N:19]=[C:18]([S:22][CH3:23])[N:17]=1)([CH3:12])([CH3:11])[CH3:10]

Participants

Conditions

Temperature: 80 °C

Procedure

To a suspension of sodium hydride (7.15 g, 179 mmol, 60% in oil) in DMSO (100 mL) was added tert-butyl cyanoacetate (24.8 g, 170 mmol) at 23° C. After the evolution of hydrogen ceased, 4-chloro-2-methylthiopyrimidine (13.7 g, 85 mmol) was added. The reaction was heated at 80° C. for 16 h. The reaction mixture was then cooled to room temperature and quenched with ice-cooled saturated ammonium chloride (300 mL). The solid was filtered and washed with water (2×200 mL). 300 mL of hexane was added to the solid and the suspension was heated at 60° C. for 1 h and then cooled to room temperature. The solid was filtered and washed with hexane to afford the title compound; 1H NMR 400 MHz (CDCl3) δ 7.82 (d, 1H), 6.74 (d, 1H), 2.63 (s, 3H), 2.61 (s, 1H), 1.52 (s, 9H); MS m/z: 266.0 (M+1).

Workup

temperatureThe reaction mixture was then cooled to room temperature
customquenched with ice-
temperaturecooled saturated ammonium chloride (300 mL)
filtrationThe solid was filtered
washwashed with water (2×200 mL)
addition300 mL of hexane was added to the solid
temperaturethe suspension was heated at 60° C. for 1 h
temperaturecooled to room temperature
filtrationThe solid was filtered
washwashed with hexane

Sources & evidence

ORD record: ord-dab79fed870249668d2e6bba91e68cef
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09314464B2

Reaction notes

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