4-Bromoanisole → 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-((4'-methoxy-[1,1'-biphenyl]-3-yl)oxy)propan-2-ol

HRID 1051450노트

반응식

HRID 1051450 반응식
[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:30])[CH2:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17](B2OC(C)(C)C(C)(C)O2)[CH:16]=1.Br[C:32]1[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:30])[CH2:13][O:14][C:15]1[CH:16]=[C:17]([C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=2)[CH:18]=[CH:19][CH:20]=1

참가 물질

6

반응물 3

HCID 77304-BromoanisoleHCID 11430Potassium CarbonateHCID 867292361-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)propan-2-ol

생성물 1

HCID 867292411-(3,4-dihydroisoquinolin-2(1H)-yl)-3-((4'-methoxy-[1,1'-biphenyl]-3-yl)oxy)propan-2-ol수율 49%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 312751,4-Dioxane용매

반응 조건

온도
120 °C

실험 절차

To a mixture of 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)propan-2-ol (250 mg, 0.61 mmol) in Dioxane (3 mL) was added 4-bromoanisole (115 mg, 0.61 mmol), 2N K2CO3 (1 mL, 2 mmol) and PdCl2(dppf)2 (20 mg, 0.025 mmol). The reaction mixture was heated at 120° C. under microwave heating conditions for 30 minutes before concentrated to remove the solvent. The residue was dissolved in ethyl acetate, washed with water with the separated organic layer dried and concentrated to yield a crude product which was purified by prep-HPLC separation to give title compound (116 mg, 49%). 1H NMR (400 MHz, MeOD): δ 7.55-7.51 (m, 2H), 7.35-7.27 (m, 4H), 7.24-7.15 (m, 3H), 7.01-6.97 (m, 2H), 6.92-6.89 (m, 1H), 4.66 (brs, 1H), 4.56-4.51 (m, 2H), 4.16-4.07 (m, 2H), 3.92 (brs, 1H), 3.83 (s, 3H), 3.58-3.48 (m, 3H), 3.32-3.22 (m, 2H), ppm; ESI-MS (m/z): 390.2 [M+1]+.

후처리

  1. temperatureheating conditions for 30 minutes
  2. concentrationbefore concentrated
  3. customto remove the solvent
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with water with the separated organic layer
  6. customdried
  7. concentrationconcentrated
  8. customto yield a crude product which
  9. customwas purified by prep-HPLC separation

출처 및 근거

ORD 기록
ord-68325b1b69104644bfeba9f3b1f7f523
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09388173B2

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