tert-Butyldimethylsilyl chloride → HCID 90022684, 화합물

HRID 1772877노트

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HRID 1772877 반응식
[C:1]([Si:5](Cl)([CH3:7])[CH3:6])([CH3:4])([CH3:3])[CH3:2].[F:9][C:10]1[CH:18]=[C:17]([OH:19])[CH:16]=[C:15]([F:20])[C:11]=1[C:12]([OH:14])=[O:13].C(N(CC)C(C)C)(C)C>C1COCC1>[F:9][C:10]1[CH:18]=[C:17]([O:19][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:7])[CH3:6])[CH:16]=[C:15]([F:20])[C:11]=1[C:12]([OH:14])=[O:13]

참가 물질

5

반응물 3

HCID 28928tert-Butyldimethylsilyl chlorideHCID 81531DiisopropylethylamineHCID 27787762,6-difluoro-4-Hydroxybenzoic Acid

생성물 1

HCID 90022684HCID 90022684, 화합물수율 12%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

tert-Butyl(chloro)dimethylsilane (6.42 g, 42.6 mmol) was added to a solution of 2,6-difluoro-4-hydroxybenzoic acid (3.09 g, 17.8 mmol) in THF (50 mL), followed by the addition of N,N-diisopropylethylamine (9.19 mL, 51.5 mmol) over 5 min. After stirring at rt for 10 min the solution was concentrated in vacuo. Purification by gradient column chromatography, eluting with 10-50% solvent A in solvent B (A=DCM, B=DCM:MeOH:AcOH 95:5:1) yielded 2,6-difluoro-4-(tert-butyldimethylsilyloxy)benzoic acid (615 mg). This material was dissolved in THF (20 mL), borane-THF complex (1.0M in THF, 6.4 mL, 6.4 mmol) was added and the solution stirred at rt for 4 h. Further borane-THF complex (1.0M in THF, 6.4 mL, 6.4 mmol) was added and the solution stirred at rt for 18.5 h before concentration in vacuo. Purification by gradient column chromatography, eluting with 0-10% EtOAc in iso-hexane yielded 2,6-difluoro-4-(tert-butyldimethylsilyloxy)benzyl alcohol (470 mg). The title compound (533 mg, 0.90 mmol) was subsequently prepared from 2,6-difluoro-4-(tert-butyldimethylsilyloxy)benzyl alcohol (356 mg, 1.30 mmol) and (IntA1) (289 mg) using the methods of (77).

후처리

  1. concentrationwas concentrated in vacuo
  2. customPurification by gradient column chromatography
  3. washeluting with 10-50% solvent A in solvent B (A=DCM, B=DCM:MeOH:AcOH 95:5:1)

출처 및 근거

ORD 기록
ord-6c26c96023464126845be57142d16e84
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09249160B2

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