Tributylphosphine → 6-[Cyclopropyl-(3-methoxy-2-methylbenzyl)carbamoyl]-7-{2-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]thiazol-5-yl}-3,9-diazabicyclo[3.3.1]non-6-ene-3,9-dicarboxylic acid di-tert-butyl ester

HRID 1096871

반응식

HRID 1096871 반응식
[Cl:1][C:2]1[C:7]([OH:8])=[C:6]([Cl:9])[CH:5]=[C:4]([CH3:10])[CH:3]=1.[C:11]([O:15][C:16]([N:18]1[CH2:25][CH:24]2[N:26]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:20]([CH2:21][C:22]([C:50]3[S:54][C:53]([O:55][CH2:56][CH2:57]O)=[N:52][CH:51]=3)=[C:23]2[C:34](=[O:49])[N:35]([CH:46]2[CH2:48][CH2:47]2)[CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([O:43][CH3:44])[C:38]=2[CH3:45])[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].P(CCCC)(CCCC)CCCC>C1(C)C=CC=CC=1.CCOCC>[C:11]([O:15][C:16]([N:18]1[CH2:25][CH:24]2[N:26]([C:27]([O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[O:28])[CH:20]([CH2:21][C:22]([C:50]3[S:54][C:53]([O:55][CH2:56][CH2:57][O:8][C:7]4[C:2]([Cl:1])=[CH:3][C:4]([CH3:10])=[CH:5][C:6]=4[Cl:9])=[N:52][CH:51]=3)=[C:23]2[C:34](=[O:49])[N:35]([CH:46]2[CH2:47][CH2:48]2)[CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([O:43][CH3:44])[C:38]=2[CH3:45])[CH2:19]1)=[O:17])([CH3:12])([CH3:13])[CH3:14]

참가 물질

6

반응물 3

HCID 13831TributylphosphineHCID 170772,6-Dichloro-4-methylphenolHCID 685707976-[Cyclopropyl-(3-methoxy-2-methylbenzyl)carbamoyl]-7-[2-(2-hydroxyethoxy)thiazol-5-yl]-3,9-diazabicyclo[3.3.1]non-6-ene-3,9-dicarboxylic acid di-tert-butyl ester

생성물 1

HCID 685710656-[Cyclopropyl-(3-methoxy-2-methylbenzyl)carbamoyl]-7-{2-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]thiazol-5-yl}-3,9-diazabicyclo[3.3.1]non-6-ene-3,9-dicarboxylic acid di-tert-butyl ester수율 76%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 3283Diethyl Ether용매

반응 조건

온도
80 °C

실험 절차

A sol. of 2,6-dichloro-p-cresol (0.55 mmol; 97 mg) in toluene (4.8 mL) was treated with compound E9 (0.37 mmol; 250 mg) followed by azodicarboxylic dipiperidide (0.73 mmol; 184 mg) and PBu3 (1.28 mmol; 0.27 mL). The reaction mixture was stirred at 80° C. After 1 h, the reaction mixture was allowed to cool to rt, diluted with Et2O (50 mL), filtrated, and the filtrate was washed with NaOH 1M (50 mL) and brine (50 mL). The org. extract was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc/heptane 30:70) yielded the title compound (0.23 g, 76%). LC-MS: tR=1.25 min; ES+: 843.29.

후처리

  1. temperatureto cool to rt
  2. filtrationfiltrated
  3. washthe filtrate was washed with NaOH 1M (50 mL) and brine (50 mL)
  4. extractionextract
  5. dry with materialwas dried over MgSO4
  6. filtrationfiltered
  7. customthe solvents were removed under reduced pressure
  8. customPurification of the residue by FC (EtOAc/heptane 30:70)

출처 및 근거

ORD 기록
ord-8113673050884606b0e167c280617300
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08138340B2

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