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

HRID 1773988노트

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HRID 1773988 반응식
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[CH2:30]([O:32][C:33](=[O:45])[CH:34]([C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[C:38](Br)[CH:37]=1)[CH3:35])[CH3:31].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH2:54]([O:61][C:62]([N:64]1[CH2:73][CH2:72][C:71]2[C:66](=[C:67](B3OC(C)(C)C(C)(C)O3)[CH:68]=[CH:69][C:70]=2[F:74])[CH2:65]1)=[O:63])[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1>C1(C)C=CC=CC=1.O.CCOCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:54]([O:61][C:62]([N:64]1[CH2:73][CH2:72][C:71]2[C:66](=[C:67]([C:38]3[CH:37]=[C:36]([CH:34]([C:33]([O:32][CH2:30][CH3:31])=[O:45])[CH3:35])[CH:41]=[CH:40][C:39]=3[O:42][CH3:43])[CH:68]=[CH:69][C:70]=2[F:74])[CH2:65]1)=[O:63])[C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=1

참가 물질

9

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 574588042-(3-Bromo-4-methoxy-phenyl)-propionic acid ethyl esterHCID 896488855-fluoro-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

생성물 1

HCID 89648690(+/-)-8-[5-(1-Ethoxycarbonyl-ethyl)-2-methoxy-phenyl]-5-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 1140Toluene용매HCID 3283Diethyl Ether용매

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온도
100 °C

실험 절차

A mixture under N2 of palladium(II)acetate (1.2 mg, 5 μmol, 0.02 eq.), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (4.2 mg, 0.01 mmol, 0.04 eq.), (±)-2-(3-bromo-4-methoxy-phenyl)-propionic acid ethyl ester (80 mg, 0.26 mmol, 1 eq.) and potassium phosphate (109 mg, 0.51 mmol, 2 eq.) in toluene (1.9 mL) and water (0.2 mL) was stirred at r.t. during 2 min. 5-Fluoro-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (147 mg, 0.26 mmol, 1 eq.) was added and the mixture was stirred at 100° C. for 18 hours. The mixture was allowed to cool to r.t., diluted with Et2O (10 mL), filtered through celite, washed with Et2O, and the filtrate was concentrated in vacuo. The residue was purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo to give the title compound as a colorless oil.

후처리

  1. temperatureto cool to r.t.
  2. filtrationfiltered through celite
  3. washwashed with Et2O
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe residue was purified by prep
  6. concentrationHPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo

출처 및 근거

ORD 기록
ord-d1c76907915f49adae84574116cc81b9
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09255090B2

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