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

HRID 575120노트

반응식

HRID 575120 반응식
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]2[C:8]([OH:21])([CH3:20])[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].[CH3:22][C:23]([OH:27])([C:25]#[CH:26])[CH3:24].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CCN(CC)CC.CC([O-])=O.CC([O-])=O.[Pd+2].[Cu]I>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]2[C:8]([OH:21])([CH3:20])[CH2:9][O:10][C:11]3[CH:18]=[CH:17][C:16]([C:26]#[C:25][C:23]([OH:27])([CH3:24])[CH3:22])=[CH:15][C:12]=3[C:13]=2[N:14]=1)=[O:4]

참가 물질

7

반응물 3

HCID 82582-Methyl-3-butyn-2-olHCID 11776TriphenylphosphineHCID 866931469-Bromo-4-hydroxy-4-methyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester

생성물 1

HCID 866931474-Hydroxy-9-(3-hydroxy-3-methyl-but-1-ynyl)-4-methyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester수율 80.3%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 167845palladium(II) acetate촉매HCID 8471Triethylamine용매

반응 조건

온도
80 °C

실험 절차

A mixture of 9-Bromo-4-hydroxy-4-methyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester (387 mg, 1.04 mmol), 2-methyl-3-butyn-2-ol (699 mg, 8.32 mmol), Pd(OAc)2 (23 mg, 0.104 mmol), CuI (39 mg, 0.208 mmol) and PPh3 (82 mg, 0.312 mmol) in Et3N (15 mL) was degassed with N2, and the mixture was stirred at 80° C. overnight. The reaction mixture was cooled to room temperature, concentrated and purified by flash column chromatography (silica gel, EtOAc in hexane from 0 to 50%) to give 4-Hydroxy-9-(3-hydroxy-3-methyl-but-1-ynyl)-4-methyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester as a yellow solid (312 mg, 80%). LC-MS (ESI & APCI): 374.3 (M+1).

후처리

  1. customwas degassed with N2
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationconcentrated
  4. custompurified by flash column chromatography (silica gel, EtOAc in hexane from 0 to 50%)

출처 및 근거

ORD 기록
ord-506bd4db4a4d4515b62656af6a0bea2e
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09034866B2

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