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

HRID 1969353
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HRID 1969353 반응식
[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]
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참가 물질

6

반응물 3

HCID 821241,4-Bis(diphenylphosphino)butaneHCID 517045Sodium AcetateHCID 591269272,6-Dichloro-5-methoxypyrimidin-4-amine

생성물 1

HCID 59126903Ethyl 6-amino-2-chloro-5-methoxypyrimidine-4-carboxylate수율 232.5%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매
HCID 702
Ethanol
용매

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온도
110 °C

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-30c109e5066446bd97fb690ab9168687
출처 데이터셋
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08426591B2

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