Hydrochloric Acid → (RS)-[3-(tert-butyl-diphenyl-silanyloxy)-2,6-difluoro-phenyl]-hydroxy-acetic acid ethyl ester

HRID 1247379

반응식

HRID 1247379 반응식
[C:1]([Si:5]([O:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=1[F:26])([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([CH3:4])([CH3:3])[CH3:2].CN(C)CCN(C)CCN(C)C.[Li]CCCC.[CH2:44]([O:46][C:47](=[O:50])[CH:48]=[O:49])[CH3:45].Cl>COCCOC.CCCCCC.C1(C)C=CC=CC=1>[CH2:44]([O:46][C:47](=[O:50])[CH:48]([C:21]1[C:22]([F:25])=[CH:23][CH:24]=[C:19]([O:18][Si:5]([C:1]([CH3:4])([CH3:2])[CH3:3])([C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:20]=1[F:26])[OH:49])[CH3:45]

참가 물질

9

반응물 5

HCID 313Hydrochloric AcidHCID 18196PentamethyldiethylenetriamineHCID 70211Ethyl oxoacetateHCID 21904942Tert-butyl-(2,4-difluoro-phenoxy)-diphenyl-silaneHCID 178418339Butyllithium

생성물 1

HCID 69290212(RS)-[3-(tert-butyl-diphenyl-silanyloxy)-2,6-difluoro-phenyl]-hydroxy-acetic acid ethyl ester수율 54%

시약·촉매·용매 3

HCID 1140Toluene용매HCID 8058Hexane용매HCID 80711,2-Dimethoxyethane용매

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온도
-70 °C

실험 절차

A solution under Ar of tert-butyl-(2,4-difluoro-phenoxy)-diphenyl-silane (102 g) and 1,1,4,7,7-pentamethyldiethylenetriamine (50.6 g) in DME (800 ml) was cooled to −70° C. before addition of 1.6 N n-BuLi in hexane (182 ml) over a period of 1 h. The yellow solution was stirred 1 h at −70° C. 50% glyoxalic acid ethylester in toluene (113 g) was added over a period of 1 h. The reaction mixture was stirred 2 h more at −70° C. before heating up over 1 h to 0° C. Sat. NH4 sol. (300 ml) was added and the pH was lowered to pH=6 with 2 N HCl. The product was extracted with AcOEt (2×400 ml). The organic layers were washed with brine (500 ml) and dried (Na2SO4) and the solvent was evaporated. CC (Hept to Hept/AcOEt 9:1) afforded 70.8 g (54%) of (RS)-[3-(tert-butyl-diphenyl-silanyloxy)-2,6-difluoro-phenyl]-hydroxy-acetic acid ethyl ester. Yellowish oil. MS 488.5 ([M+H]+).

후처리

  1. stirringThe reaction mixture was stirred 2 h more at −70° C.
  2. temperaturebefore heating up over 1 h to 0° C
  3. extractionThe product was extracted with AcOEt (2×400 ml)
  4. washThe organic layers were washed with brine (500 ml)
  5. dry with materialdried (Na2SO4)
  6. customthe solvent was evaporated

출처 및 근거

ORD 기록
ord-c19e0c27070343f4967fb8f61c10d3c2
출처 데이터셋
uspto-grants-2006_10
특허 번호
US07129238B2

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