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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
ノート
印刷プレビュー

反応式

HRID 2037377 の反応式
[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]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

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

生成物 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 ester収率 69.2%

試薬・触媒・溶媒 2

HCID 6342
Acetonitrile
溶媒
HCID 8857Ethyl Acetate溶媒

反応条件

温度
65 °C

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-fdf9a71874924bc78955de01776ad3af
出典データセット
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08575200B2

反応ノート

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