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Potassium Carbonate → 2-{2-Ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-malonic acid dimethyl ester

HRID 2037377
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HRID 2037377 반응식
[CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[C:17]([CH2:21][CH:22]([CH3:24])[CH3:23])=[CH:16][N:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:25])[C:4]=1[OH:26])[CH3:2].C([O-])([O-])=O.[K+].[K+].Cl[CH:34]([C:39]([O:41][CH3:42])=[O:40])[C:35]([O:37][CH3:38])=[O:36]>C(#N)C.CC(=O)OCC>[CH3:38][O:37][C:35](=[O:36])[CH:34]([O:26][C:4]1[C:5]([CH3:25])=[CH:6][C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[C:17]([CH2:21][CH:22]([CH3:23])[CH3:24])=[CH:16][N:15]=3)[O:11][N:10]=2)=[CH:8][C:3]=1[CH2:1][CH3:2])[C:39]([O:41][CH3:42])=[O:40]
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HCID 11430Potassium CarbonateHCID 120070Dimethyl chloromalonateHCID 1363440752-Ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenol

생성물 1

HCID 686304192-{2-Ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-malonic acid dimethyl ester수율 69.2%

시약·촉매·용매 2

HCID 6342
Acetonitrile
용매
HCID 8857Ethyl Acetate용매

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온도
65 °C

실험 절차

To a solution of the compound of Example 32 (100 mg, 285 μmol) in acetonitrile (2 mL), K2CO3 (56 mg, 427 μmol) followed by dimethyl chloromalonate (57 mg, 341 μmol) is added. The mixture is stirred at 65° C. for 18 h. The mixture is diluted with EA and washed with water. The org. extract is concentrated and the crude product is purified on prep. TLC plates using heptane:EA 4:1 to give 2-{2-ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-malonic acid dimethyl ester (95 mg) as a colourless oil; LC-MS: tR=1.17 min, [M+H]+=482.01. This material (95 mg, 197 μmol) is dissolved in ethanol (10 mL) and treated with NaBH4 (60 mg, 1.58 mmol). The mixture is stirred at 60° C. for 1 h before the reaction is quenched with water. The mixture is extracted twice with EA and the combined extracts are concentrated. The crude product is purified on prep. TLC plates using heptane:EA 1:1 to give the title compound (44 mg) as a colourless oil; LC-MS: tR=1.02 min, [M+H]+=426.01; 1H NMR (CDCl3): δ1.00 (d, J=6.5 Hz, 6H), 1.31 (t, J=7.3 Hz, 3H), 1.95 (hept, J=6.3 Hz, 1H), 2.08 (t br, J=5.5 Hz, 2H), 2.42 (s, 3H), 2.47 (s, 3H), 2.63 (d, J=7.0 Hz, 2H), 2.80 (q, J=7.5 Hz, 2H), 3.91-4.05 (m, 4H), 4.19 (quint, J=4.5 Hz, 1H), 7.95 (s, 1H), 7.98 (s, 1H), 8.10 (s, 1H), 8.55 (s, 1H).

후처리

  1. additionis added
  2. washwashed with water
  3. extractionextract
  4. concentrationis concentrated
  5. customthe crude product is purified on prep

출처 및 근거

ORD 기록
ord-fdf9a71874924bc78955de01776ad3af
출처 데이터셋
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08575200B2

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