1,4-Bis(diphenylphosphino)butane → Ethyl 6-amino-2-chloro-5-methoxypyrimidine-4-carboxylate

HRID 1969353Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([O:9][CH3:10])=[C:4](Cl)[N:3]=1.[C:12]([O-:15])(=[O:14])C.[Na+].[CH:17]1C=CC(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)=C[CH:18]=1>C(O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:17]([O:15][C:12]([C:4]1[C:5]([O:9][CH3:10])=[C:6]([NH2:8])[N:7]=[C:2]([Cl:1])[N:3]=1)=[O:14])[CH3:18]

Participants

Conditions

Temperature: 110 °C

Procedure

2,6-Dichloro-5-methoxypyrimidin-4-ylamine (5.0 g, 26 mmol) was combined in 75 mL absolute ethanol with sodium acetate (2.1 g, 26 mmol), palladium acetate (280 mg, 0.91 mmol) and DPPB (1.1 g, 2.6 mmol) in a 300 mL stirred pressure reactor. The reactor was purged and pressurized to 300 psi with carbon monoxide, and heated at 110° C. for 7 h. The volatiles were removed under vacuum and the residue was taken up in ethyl acetate and water. The aqueous phase was extracted with an additional ethyl acetate; and the combined extracts were washed with brine, dried and evaporated. The residue was purified by flash chromatography on silica gel (0-30% ethyl acetate gradient in hexanes) to give the title compound (1.4 g, 23% yield): mp 118-119° C. 1H NMR (CDCl3) δ 6.18 (br s, 2H), 4.45 (q, 2H), 3.91 (s, 3H), 1.42 (t, 3H).

Workup

customThe reactor was purged
customThe volatiles were removed under vacuum
extractionThe aqueous phase was extracted with an additional ethyl acetate
washand the combined extracts were washed with brine
customdried
customevaporated
customThe residue was purified by flash chromatography on silica gel (0-30% ethyl acetate gradient in hexanes)

Sources & evidence

ORD record: ord-30c109e5066446bd97fb690ab9168687
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08426591B2

Reaction notes

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