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1,2-Dimethoxyethane → [5-(5-Ethyl-6-methoxy-2-methyl-pyridin-3-yl)-thiophen-2-ylmethyl]-carbamic acid tert-butyl ester

HRID 1921464
ノート
印刷プレビュー

反応式

HRID 1921464 の反応式
C[C:2]1(C)[C:7]([CH3:9])(C)[CH:6]=[N:5][C:4](B2OCCO2)=[CH:3]1.[C:16](=[O:19])([O-])[O-].[Cs+].[Cs+].[C:22]([O:26][C:27](=[O:36])[NH:28][CH2:29][C:30]1[S:31]C(Br)=[CH:33][CH:34]=1)([CH3:25])([CH3:24])[CH3:23].[C:37](OCC)(=O)[CH3:38].[CH3:43]OCCOC>O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[C:22]([O:26][C:27](=[O:36])[NH:28][CH2:29][C:30]1[S:31][C:9]([C:7]2[C:6]([CH3:43])=[N:5][C:4]([O:19][CH3:16])=[C:3]([CH2:37][CH3:38])[CH:2]=2)=[CH:33][CH:34]=1)([CH3:23])([CH3:24])[CH3:25]
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

8

反応物 5

HCID 80711,2-DimethoxyethaneHCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 2779810tert-Butyl ((5-bromothiophen-2-yl)methyl)carbamateHCID 866103514,4,5,5-Tetramethyl-[1,3,2-dioxaborolan-2-yl)pyridine

生成物 1

HCID 67492643[5-(5-Ethyl-6-methoxy-2-methyl-pyridin-3-yl)-thiophen-2-ylmethyl]-carbamic acid tert-butyl ester

試薬・触媒・溶媒 2

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 962Water溶媒

反応条件

温度
110 °C

実験手順

To a nitrogen flushed mixture of 3-ethyl-2-methoxy-6-methyl-5-(4,4,5,5-tetramethyl-[1,3,2-dioxaborolan-2-yl)pyridine (1.0 g, 3.6 mmol), cesium carbonate (3.52 g, 11 mmol), and (5-bromo-thiophen-2-ylmethyl)-carbamic acid tert-butyl ester (1.2 g, 4.0 mmol) in 1,2-dimethoxyethane (20 mL) and water (4 mL) is added palladium tetrakis(triphenylphosphine) (290 mg, 0.25 mmol) and the reaction mixture is heated to about 110° C. After maintaining the reaction mixture at 110° C. for 12 hr, the mixture is cooled, poured into ethyl acetate (50 mL) and washed with water and brine, dried over sodium sulfate, filtered and concentrated. The residue is chromatographed on SiO2, eluting with heptane-30% ethyl acetate to afford 0.98 g of [5-(5-ethyl-6-methoxy-2-methyl-pyridin-3-yl)-thiophen-2-ylmethyl]-carbamic acid tert-butyl ester. A solution of this ester in MeOH is then treated with saturated HCl in EtOAc (50 mL) and heated to about 75° C. After 6 hr at 75° C., the mixture is concentrated, and triturated with acetonitrile/water to afford 2.8 g of 5-(5-aminomethylthiophen-2-yl)-3-ethyl-6-methyl-1H-pyridin-2-one hydrochloride as a white solid (78% yield). LC/MS: RT 1.77 min; m/e 249 (M+H).

後処理

  1. customTo a nitrogen flushed
  2. temperatureAfter maintaining the reaction mixture at 110° C. for 12 hr
  3. temperaturethe mixture is cooled
  4. washwashed with water and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue is chromatographed on SiO2
  9. washeluting with heptane-30% ethyl acetate

出典と根拠

ORDレコード
ord-ac1cb3840ee14274a5b3a337fb8df171
出典データセット
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08173682B2

反応ノート

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