Potassium Phosphate, Tribasic → Tert-butyl 4-(bicyclo[4.1.0]heptan-1-ylmethoxy)-5-cyclopropyl-2-fluorobenzoate

HRID 1849783노트

반응식

HRID 1849783 반응식
[C:1]12([CH2:8][O:9][C:10]3[C:22](Cl)=[CH:21][C:13]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[C:12]([F:24])[CH:11]=3)[CH2:7][CH:6]1[CH2:5][CH2:4][CH2:3][CH2:2]2.[CH:25]1(B(O)O)[CH2:27][CH2:26]1.F[B-](F)(F)F.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]12([CH2:8][O:9][C:10]3[C:22]([CH:25]4[CH2:27][CH2:26]4)=[CH:21][C:13]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[C:12]([F:24])[CH:11]=3)[CH2:7][CH:6]1[CH2:5][CH2:4][CH2:3][CH2:2]2

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborateHCID 86703665Tert-butyl 4-(bicyclo[4.1.0]heptan-1-ylmethoxy)-5-chloro-2-fluorobenzoate

생성물 1

HCID 86703666Tert-butyl 4-(bicyclo[4.1.0]heptan-1-ylmethoxy)-5-cyclopropyl-2-fluorobenzoate수율 75%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 1140Toluene용매

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온도
140 °C

실험 절차

In a sealed tube containing tert-butyl 4-(bicyclo[4.1.0]heptan-1-ylmethoxy)-5-chloro-2-fluorobenzoate (1.30 g, 3.70 mmol), cyclopropylboronic acid (0.47 g, 5.50 mmol), tricyclohexylphosphine tetrafluoroborate (0.27 g, 0.74 mmol) and palladium acetate (0.08 g, 0.37 mmol) and potassium phosphate (3.13 g, 14.8 mmol) in toluene (20 mL) and water (2.0 mL) was bubbled with a nitrogen atmosphere for 10 minutes. The reaction mixture was heated to 140° C. for 6 hours and cooled to ambient temperature. The solvent was concentrated in vacuo to dryness. The crude residue was purified column chromatography (10% gradient ethyl acetate in hexanes) afforded the title compound as a colorless solid (1.00 g, 75%): 1H NMR (300 MHz, CDCl3) 7.37 (d, J=8.5 Hz, 1H), 6.42 (d, J=12.8 Hz, 1H), 3.61 (d, J=9.1 Hz, 1H), 3.78 (d, J=9.1 Hz, 1H), 1.96-1.52 (m, 7H), 1.55 (s, 9H), 0.92-0.82 (m, 4H), 0.67-0.61 (m, 4H), 0.38-0.33 (m, 1H).

후처리

  1. customwas bubbled with a nitrogen atmosphere for 10 minutes
  2. temperaturecooled to ambient temperature
  3. concentrationThe solvent was concentrated in vacuo to dryness
  4. customThe crude residue was purified column chromatography (10% gradient ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-41906bff08654de1af0bb5341bf14897
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952169B2

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