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

HRID 1849783ノート

反応式

HRID 1849783 の反応式
[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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
140 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-41906bff08654de1af0bb5341bf14897
出典データセット
uspto-grants-2015_02
特許番号
US08952169B2

反応ノート

読み込み中…