Dicyclohexylamine → (2-Fluoro-5-methyl-phenyl)-acetic acid tert-butyl ester

HRID 521446

반응식

HRID 521446 반응식
C1(NC2CCCCC2)CCCCC1.C([Li])CCC.[C:19]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])(=[O:21])[CH3:20].Br[C:28]1[CH:29]=[C:30]([CH3:35])[CH:31]=[CH:32][C:33]=1[F:34]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>[C:23]([O:22][C:19](=[O:21])[CH2:20][C:28]1[CH:29]=[C:30]([CH3:35])[CH:31]=[CH:32][C:33]=1[F:34])([CH3:26])([CH3:25])[CH3:24]

참가 물질

8

반응물 4

HCID 7582DicyclohexylamineHCID 10908tert-Butyl acetateHCID 967453-Bromo-4-fluorotolueneHCID 178418339Butyllithium

생성물 1

HCID 67076289(2-Fluoro-5-methyl-phenyl)-acetic acid tert-butyl ester수율 81.9%

시약·촉매·용매 3

HCID 2734635Tri-tert-butylphosphine tetrafluoroborate촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

실험 절차

In analogy to the procedure described in M. Jørgensen et al., J. Am. Chem. Soc. 124 (2002), 12557-12565, in a first flask, dicyclohexylamine (3.06 g, 16.9 mmol) was dissolved in toluene and cooled in an ice bath. n-Butyllithium (6.14 ml, 2.5 M solution in hexane) was added. After 5 min, tert-butyl acetate (1.78 g, 15.3 mmol) was added slowly. A second flask was charged with tri-(tert-butyl)phosphonium tetrafluoroborate (83 mg, 0.30 mmol) and tris(dibenzylideneacetone)dipalladium(0) (146 mg, 0.153 mmol) and thoroughly flushed with argon. Toluene (100 ml) was added, followed by 3-bromo-4-fluoro-toluene (2.90 g, 15.3 mmol) and by the contents of the first flask. After stirring overnight, the formed suspension was filtered over a small plug of silica gel which was washed repeatedly with diethyl ether. The filtrates were evaporated in vacuo and the residue was purified by silica gel chromatography (HEP/EA gradient) to give 2.81 g of (2-fluoro-5-methyl-phenyl)-acetic acid tert-butyl ester.

후처리

  1. temperaturecooled in an ice bath
  2. customthoroughly flushed with argon
  3. additionToluene (100 ml) was added
  4. filtrationthe formed suspension was filtered over a small plug of silica gel which
  5. washwas washed repeatedly with diethyl ether
  6. customThe filtrates were evaporated in vacuo
  7. customthe residue was purified by silica gel chromatography (HEP/EA gradient)

출처 및 근거

ORD 기록
ord-b64fd81e3c6f4860b2d124b82721a188
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09328071B2

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