Sodium Hydroxide → Methyl 2-chloro-6-cyclopropylpyrimidine-4-carboxylate

HRID 634211Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[N:3]=1.CC(N)[CH2:15][C:16]1[CH:21]=CC=CC=1.OP(O)(O)=O.[Br-].C1([Zn+])CC1.[OH-].[Na+]>CCOC(C)=O>[Cl:1][C:2]1[N:3]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[CH:5]=[C:6]([CH:21]2[CH2:16][CH2:15]2)[N:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

In a 5 mL glass microwave tube methyl 2,4-dichloropyrimidine-6-carboxylate (621 mg, 3.00 mmol) (Astatech Inc.) and Amphos (53.1 mg, 0.075 mmol) were treated with cyclopropylzinc(II) bromide (Rieke, 0.5 M in THF) (1.2 mL, 6.00 mmol) via syringe under an atmosphere of argon. The solution was then heated in the microwave at 80° C. for 20 min. The mixture was treated with EtOAc and 1N NaOH resulting in a white suspension as the zinc hydroxide salts precipitated out. The suspension was extracted with EtOAc (50 mL) a second time and washed with brine and dried over Na2SO4, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 100% DCM) to give methyl 2-chloro-6-cyclopropylpyrimidine-4-carboxylate (254 mg, 40%) as a clear, colorless, viscous oil. MS (ESI, pos. ion) m/z: 213.1 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 7.77 (1H, s), 3.99-4.04 (3H, m), 2.06-2.15 (1H, m), 1.20-1.31 (4H, m).

Workup

customprecipitated out
extractionThe suspension was extracted with EtOAc (50 mL) a second time
washwashed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified with silica gel chromatography (eluting with 100% DCM)

Sources & evidence

ORD record: ord-3c73bbf3e5424e81af68ba47a91bf01d
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321756B2

Reaction notes

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