Potassium Phosphate, Tribasic → 4-(4-(difluoromethoxy)phenyl)-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-one

HRID 1044412

反応式

HRID 1044412 の反応式
[F:1][CH:2]([F:19])[O:3][C:4]1[CH:9]=[CH:8][C:7](B2OC(C)(C)C(C)(C)O2)=[CH:6][CH:5]=1.Cl[C:21]1[CH:26]=[CH:25][N:24]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH2:34][C:35]([OH:38])([CH3:37])[CH3:36])=[C:29]([O:39][CH3:40])[CH:28]=2)[C:23](=[O:41])[CH:22]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:19][CH:2]([F:1])[O:3][C:4]1[CH:5]=[CH:6][C:7]([C:21]2[CH:26]=[CH:25][N:24]([C:27]3[CH:32]=[CH:31][C:30]([O:33][CH2:34][C:35]([OH:38])([CH3:37])[CH3:36])=[C:29]([O:39][CH3:40])[CH:28]=3)[C:23](=[O:41])[CH:22]=2)=[CH:8][CH:9]=1

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 220323032-(4-(Difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 585802944-chloro-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-one

生成物 1

HCID 469112064-(4-(difluoromethoxy)phenyl)-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-one収率 36.7%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

A mixture of 2-(4-(difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Part A (62.6 mg, 0.23 mmol), 4-chloro-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-one Part D of Procedure 9 (50 mg, 0.15 mmol), Potassium phosphate tribasic (65.6 mg, 0.31 mmol), Palladium (II) acetate (1.7 mg, 7.7 μmol), and 2-DICYCLOHEXYLPHOSPHINO-2′,6′-DIMETHOXY-1,1′-BIPHENYL (3.1 mg, 7.72 μmol) in Toluene (1.4 mL) and Water (0.15 mL) was stirred at 100° C. for 16 h. The mixture was filtered, diluted with EtOAc, washed with sat. NaHCO3, dired (MgSO4), and concentrated. The crude was purified using HPLC (Phen Luna Axia C18 5μ 10:90:0.1 to 90:10:0.1 MeOH—H2O-TFA to afford 4-(4-(difluoromethoxy)phenyl)-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-one B-9 (26.26 mg, 0.057 mmol, 36.7% yield) as a white solid. LC/MS 432 (M+H)+, tR 0.87 min (method 5). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.63 (2H, d), 7.42 (1H, d, J=7.04 Hz), 7.24 (2H, d, J=8.58 Hz), 6.95-7.03 (2H, m), 6.90-6.93 (1H, m), 6.86 (1H, s), 6.48 (1H, d, J=7.26 Hz), 6.40-6.78 (1H, m), 3.88 (3H, s), 3.87 (2H, s), 1.37 (6H, s)

後処理

  1. filtrationThe mixture was filtered
  2. additiondiluted with EtOAc
  3. washwashed with sat. NaHCO3, dired (MgSO4)
  4. concentrationconcentrated
  5. customThe crude was purified

出典と根拠

ORDレコード
ord-625410ad8fed44d1bbc67cf304a12510
出典データセット
uspto-grants-2013_10
特許番号
US08563583B2

関連ノート

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