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(4-Chlorophenyl)acetic acid → 1-[5-Bromo-2,3-difluoro-4-(trimethylsilyl)phenyl]-2-(4-chlorophenyl)ethanone

HRID 1879632
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HRID 1879632 반응식
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][C:19]([OH:21])=O)=[CH:14][CH:13]=1.[Br:22][C:23]1[C:24]([Si:35]([CH3:38])([CH3:37])[CH3:36])=[C:25]([F:34])[C:26]([F:33])=[C:27]([CH:32]=1)C(OC)=O>C1COCC1.Cl>[Br:22][C:23]1[C:24]([Si:35]([CH3:38])([CH3:37])[CH3:36])=[C:25]([F:34])[C:26]([F:33])=[C:27]([C:19](=[O:21])[CH2:18][C:15]2[CH:14]=[CH:13][C:12]([Cl:11])=[CH:17][CH:16]=2)[CH:32]=1
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참가 물질

6

반응물 3

HCID 15880(4-Chlorophenyl)acetic acidHCID 2724254Sodium bis(trimethylsilyl)amideHCID 58538053Methyl 5-bromo-2,3-difluoro-4-(trimethylsilyl)benzoate

생성물 1

HCID 585380691-[5-Bromo-2,3-difluoro-4-(trimethylsilyl)phenyl]-2-(4-chlorophenyl)ethanone

시약·촉매·용매 2

HCID 313Hydrochloric Acid용매
HCID 8028
Tetrahydrofuran
용매
3회

실험 절차

To a solution of NaHMDS (1.0 M in THF, 7.7 mL, 7.7 mmol) in anhydrous THF (25 mL) at −78° C. was added a solution of 4-chlorophenylacetic acid (0.528 g, 3.09 mmol) in anhydrous THF (25 mL) over 10 minutes. The solution was stirred for 5 minutes, then a solution of the product of Step C (4.16 g, 7.8 mmol) in THF (25 mL) was added drop wise over 10 minutes. The mixture was stirred at −78° C. for two hours. The mixture was diluted with 2N HCl (aq, 50 mL), then the product was extracted into EtOAc. The organics were dried over Na2SO4, filtered, then concentrated. The resulting residue was purified by silica gel chromatography eluting with 0-50% toluene/hexanes to afford the title compound. 1H NMR (600 MHz, CDCl3): δ 7.74 (dd, J=5.3, 1.8 Hz, 1H); 7.31 (d, J=8.2 Hz, 2H); 7.16 (d, J=8.5 Hz, 2H); 4.22 (s, 2H); 0.48 (s, 9H).

후처리

  1. stirringThe mixture was stirred at −78° C. for two hours
  2. extractionthe product was extracted into EtOAc
  3. dry with materialThe organics were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was purified by silica gel chromatography
  7. washeluting with 0-50% toluene/hexanes

출처 및 근거

ORD 기록
ord-6eb1d8250863439a848c0c51531978a4
출처 데이터셋
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08318667B2

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