Potassium Phosphate, Tribasic → (+/-)-5-Fluoro-8-[2-methoxy-4-(1-methoxycarbonyl-ethoxy)-phenyl]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

HRID 1773990노트

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HRID 1773990 반응식
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[CH2:30]([O:37][C:38]([N:40]1[CH2:49][CH2:48][C:47]2[C:42](=[C:43](B3OC(C)(C)C(C)(C)O3)[CH:44]=[CH:45][C:46]=2[F:50])[CH2:41]1)=[O:39])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:68][O:69][C:70](=[O:83])[CH:71]([O:73][C:74]1[CH:79]=[CH:78][C:77](Br)=[C:76]([O:81][CH3:82])[CH:75]=1)[CH3:72]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:30]([O:37][C:38]([N:40]1[CH2:49][CH2:48][C:47]2[C:42](=[C:43]([C:77]3[CH:78]=[CH:79][C:74]([O:73][CH:71]([C:70]([O:69][CH3:68])=[O:83])[CH3:72])=[CH:75][C:76]=3[O:81][CH3:82])[CH:44]=[CH:45][C:46]=2[F:50])[CH2:41]1)=[O:39])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 896488855-fluoro-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl esterHCID 89649485Methyl 2-(4-bromo-3-methoxyphenoxy)propanoate

생성물 1

HCID 118353171(+/-)-5-Fluoro-8-[2-methoxy-4-(1-methoxycarbonyl-ethoxy)-phenyl]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 1140Toluene용매2회

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온도
100 °C

실험 절차

A mixture under N2 of palladium (II) acetate (0.4 mg, 2 μmol, 0.01 eq.), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (1.7 mg, 4 μmol, 0.02 eq.), 5-fluoro-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (95 mg, 0.20 mmol, 1.00 eq.) and potassium phosphate (85 mg, 0.40 mmol, 2.00 eq.) in toluene (0.6 mL) and water (0.035 mL) was stirred at r.t. for 2 min. A solution of (±)-2-(4-Bromo-3-methoxy-phenoxy)-propionic acid methyl ester (58 mg, 0.2 mmol, 1.00 eq.) in toluene (0.6 mL) was added and the mixture was stirred at 100° C. for 2 days. The mixture was allowed to cool to r.t., filtered through celite and concentrated in vacuo. The crude residue, redissolved in MeCN (1.5 mL) and formic acid (0.2 mL), was purified by prep. HPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, acidic conditions) and evaporated to give the title compound as a colorless oil.

후처리

  1. temperatureto cool to r.t.
  2. filtrationfiltered through celite and
  3. concentrationconcentrated in vacuo
  4. dissolutionThe crude residue, redissolved in MeCN (1.5 mL)
  5. customformic acid (0.2 mL), was purified by prep
  6. customHPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, acidic conditions) and evaporated

출처 및 근거

ORD 기록
ord-088b3609641a4c21b9cb4036de0a68f3
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09255090B2

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