2-Methyl-3-butyn-2-ol → 9-(3-Hydroxy-3-methyl-but-1-ynyl)-4-methoxycarbonylmethyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester

HRID 575124ノート

反応式

HRID 575124 の反応式
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]2[CH:8]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[CH2:9][O:10][C:11]3[CH:18]=[CH:17][C:16](Br)=[CH:15][C:12]=3[C:13]=2[N:14]=1)=[O:4].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH3:44][C:45]([OH:49])([C:47]#[CH:48])[CH3:46]>CN(C=O)C.[Cu]I>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]2[CH:8]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[CH2:9][O:10][C:11]3[CH:18]=[CH:17][C:16]([C:48]#[C:47][C:45]([OH:49])([CH3:46])[CH3:44])=[CH:15][C:12]=3[C:13]=2[N:14]=1)=[O:4]

参加物

6

反応物 3

HCID 82582-Methyl-3-butyn-2-olHCID 11776TriphenylphosphineHCID 866931499-Bromo-4-methoxycarbonylmethyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester

生成物 1

HCID 866931489-(3-Hydroxy-3-methyl-but-1-ynyl)-4-methoxycarbonylmethyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester収率 77%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

To a stirred mixture of 9-Bromo-4-methoxycarbonylmethyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester (90 mg, 0.22 mmol) in TEA (5 mL) and DMF (1 mL) were added Pd(PPh3)Cl2 (15 mg, 0.021 mmol), PPh3 (17.2 mg, 0.065 mmol), CuI (8.3 mg, 0.043 mmol) and 2-methylbut-3-yn-2-ol (92 mg, 1.09 mmol). The reaction mixture was degassed with N2 and heated to 80° C. in a microwave reactor for 1.5 h. Then the mixture was cooled to room temperature, EtOAc was added. The mixture was filtered through Celite. The filtrate was washed with saturated brine, dried over Na2SO4, filtered, concentrated in vacuo, and purified by flash column chromatography (silica gel, EtOAc in hexane from 10% to 20%) to afford 9-(3-Hydroxy-3-methyl-but-1-ynyl)-4-methoxycarbonylmethyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester (70 mg, 77%) as a light yellow solid. LC-MS (ESI & APCI): 416.7 (M+1).

後処理

  1. customThe reaction mixture was degassed with N2
  2. temperatureThen the mixture was cooled to room temperature
  3. additionEtOAc was added
  4. filtrationThe mixture was filtered through Celite
  5. washThe filtrate was washed with saturated brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified by flash column chromatography (silica gel, EtOAc in hexane from 10% to 20%)

出典と根拠

ORDレコード
ord-68ddfa13846449209fbb785e223866e9
出典データセット
uspto-grants-2015_05
特許番号
US09034866B2

反応ノート

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