Sodium Carbonate → 5-(5-Ethoxycarbonylmethyl-2-methoxy-phenyl)-8-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

HRID 1773985노트

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HRID 1773985 반응식
[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[C:14]([F:22])[CH:15]=[CH:16][C:17]=2Br)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:23]([O:25][C:26](=[O:45])[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=1)[CH3:24].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.CO.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[C:14]([F:22])[CH:15]=[CH:16][C:17]=2[C:30]2[CH:29]=[C:28]([CH2:27][C:26]([O:25][CH2:23][CH3:24])=[O:45])[CH:33]=[CH:32][C:31]=2[O:34][CH3:35])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 58120060[4-Methoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl esterHCID 89649301Benzyl 5-bromo-8-fluoro-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

생성물 1

HCID 1183531675-(5-Ethoxycarbonylmethyl-2-methoxy-phenyl)-8-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

시약·촉매·용매 2

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 70394911MeOH toluene water용매

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온도
100 °C

실험 절차

To a mixture under N2 of 5-bromo-8-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (529 mg, 1.45 mmol, 1.00 eq.), [4-methoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl ester (659 mg, 1.45 mmol, 1.00 eq.) and sodium carbonate (616 mg, 5.81 mmol, 4.00 eq.) in toluene/MeOH/water 20:4:1 (29 mL), tetrakis(triphenylphosphine) palladium (0) (84 mg, 0.07 mmol, 0.05 eq.) was added and the mixture was stirred at 100° C. for 18 hours. The mixture was allowed to cool to r.t. and concentrated in vacuo. The residue was partitioned between AcOEt (60 mL) and water (60 mL). The layers were separated. The org. phase was washed with sat. aq. NaCl soln. (1×60 mL), dried over MgSO4 and filtered through Celite. The filtrate was concentrated in vacuo. The residue was purified by flashmaster (column: 50 g, flow: 40 mL/min, 40 fractions of 40 mL, Heptane 100% to Heptane+30% AcOEt) to yield the title compound as a yellow oil.

후처리

  1. temperatureto cool to r.t.
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between AcOEt (60 mL) and water (60 mL)
  4. customThe layers were separated
  5. washphase was washed with sat. aq. NaCl soln
  6. dry with material(1×60 mL), dried over MgSO4
  7. filtrationfiltered through Celite
  8. concentrationThe filtrate was concentrated in vacuo
  9. customThe residue was purified by flashmaster (column: 50 g, flow: 40 mL/min, 40 fractions of 40 mL, Heptane 100% to Heptane+30% AcOEt)

출처 및 근거

ORD 기록
ord-6ba264f4f2a54488bc297843322edc52
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09255090B2

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