Potassium Phosphate, Tribasic → HCID 178450652, 화합물

HRID 1849677노트

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HRID 1849677 반응식
Cl[C:2]1[C:3]([O:16][CH2:17][C@H:18]2[CH2:23][CH2:22][C@H:21]([CH3:24])[CH2:20][CH2:19]2)=[CH:4][C:5]([F:15])=[C:6]([CH:14]=1)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[CH:25]1(B(O)O)[CH2:27][CH2:26]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].F[B-](F)(F)F.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:25]1([C:2]2[C:3]([O:16][CH2:17][C@H:18]3[CH2:23][CH2:22][C@H:21]([CH3:24])[CH2:20][CH2:19]3)=[CH:4][C:5]([F:15])=[C:6]([CH:14]=2)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:27][CH2:26]1

참가 물질

7

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborateHCID 178450706HCID 178450706, 화합물

생성물 1

HCID 178450652HCID 178450652, 화합물수율 90.4%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 22272177Toluene water용매

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온도
110 °C

실험 절차

To a solution of tert-butyl 5-chloro-2-fluoro-4-((trans-4-methylcyclohexyl)-methoxy)-benzoate (6.48 g, 18.16 mmol) in toluene-water (40 mL, v/v 20:1) was added cyclopropylboronic acid (2.34 g, 27.26 mmol) and tribasic potassium phosphate (17.37, 81.84 mmol). The reaction mixture was sparged with argon for 10 minutes and then charged with tricyclohexylphosphine tetrafluoroborate (1.35 g, 3.67 mmol) and palladium acetate (0.41 g, 1.82 mmol). The mixture was heated at 110° C. for 72 hours, then cooled to ambient temperature; filtered through a pad of diatomaceous earth and washed with ethyl acetate. The filtrate was concentrated in vacuo, and the residue was purified by column chromatography (0% to 10% ethyl acetate) to give the title compound (5.95 g, 90%): 1H NMR (300 MHz, CDCl3) δ 7.37 (d, J=8.4 Hz, 1H), 6.50 (d, J=12.8 Hz, 1H), 3.78 (d, J=6.1 Hz, 2H), 1.91-1.70 (m, 8H), 1.56 (s, 9H), 1.41-129 (m, 2H), 1.14-0.95 (m, 6H), 0.65-0.60 (m, 2H).

후처리

  1. customThe reaction mixture was sparged with argon for 10 minutes
  2. temperaturecooled to ambient temperature
  3. filtrationfiltered through a pad of diatomaceous earth
  4. washwashed with ethyl acetate
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by column chromatography (0% to 10% ethyl acetate)

출처 및 근거

ORD 기록
ord-ab9be3793d3f4007afc95de0f1e86e19
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952169B2

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