Acetic Acid → 5-(2-chloro-3-methoxy-phenyl)-1-(2-fluoro-6-methyl-benzyl)-6-methyl-1H-pyrimidine-2,4-dione

HRID 1617437ノート

反応式

HRID 1617437 の反応式
[F:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19](F)(F)F)[C:3]=1[CH2:4][N:5]1[C:10]([CH3:11])=[C:9](I)[C:8](=[O:13])[NH:7][C:6]1=[O:14].[Cl:23][C:24]1[C:29]([O:30][CH3:31])=[CH:28][CH:27]=[CH:26][C:25]=1B1OC(C)(C)C(C)(C)O1.[OH-].[Na+].C(O)(=O)C>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:23][C:24]1[C:29]([O:30][CH3:31])=[CH:28][CH:27]=[CH:26][C:25]=1[C:9]1[C:8](=[O:13])[NH:7][C:6](=[O:14])[N:5]([CH2:4][C:3]2[C:15]([CH3:19])=[CH:16][CH:17]=[CH:18][C:2]=2[F:1])[C:10]=1[CH3:11]

参加物

7

反応物 4

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 426062771-[2-fluoro-6-(trifluoromethyl)benzyl]-5-iodo-6-methylpyrimidine-2,4(1H,3H)-dioneHCID 450369072-(2-Chloro-3-methoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane

生成物 1

HCID 582393035-(2-chloro-3-methoxy-phenyl)-1-(2-fluoro-6-methyl-benzyl)-6-methyl-1H-pyrimidine-2,4-dione収率 70%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒

反応条件

温度
45 °C

実験手順

Compound 1b (80 g, 0.19 mol), 7a (60.22 g, 0.22 mol), HP(t-Bu)3BF4 (13.01 g, 44.85 mmol), and Pd2(dba)3 (13.69 g, 14.95 mmol) were charged to the reaction vessel and purged with an inert atmosphere. Degassed THF (560 mL) was added followed by NaOH (31.45 g, 0.56 mol) in degassed water (128.8 mL) and the reaction warmed to 45° C. After 2 hours acetic acid (56 mL) was added and stirred for 15 minutes. After settling, the layers were separated and the organic layer was filtered through celite, rinsing with hot THF (2×160 mL). The filtrate was concentrated in vacuo to a slurry, to which was added N-acetyl cysteine (15.84 g) as a solution in water (160 mL) and ethanol (640 mL) and stirred for 2 hours at 75° C. under an inert atmosphere. The slurry was cooled to RT, and the solids filtered off, washed with ethanol:water (8:2, 2×160 mL) to give 5-(2-chloro-3-methoxy-phenyl)-1-(2-fluoro-6-methyl-benzyl)-6-methyl-1H-pyrimidine-2,4-dione 7b as a white solid (58.6 g, 0.13 mol, 70%).

後処理

  1. custompurged with an inert atmosphere
  2. additionDegassed THF (560 mL) was added
  3. customthe layers were separated
  4. filtrationthe organic layer was filtered through celite
  5. washrinsing with hot THF (2×160 mL)
  6. concentrationThe filtrate was concentrated in vacuo to a slurry, to which
  7. additionwas added N-acetyl cysteine (15.84 g) as a solution in water (160 mL)
  8. stirringethanol (640 mL) and stirred for 2 hours at 75° C. under an inert atmosphere
  9. temperatureThe slurry was cooled to RT
  10. filtrationthe solids filtered off
  11. washwashed with ethanol:water (8:2, 2×160 mL)

出典と根拠

ORDレコード
ord-38fd1da5b8d64dacb745b2229c790798
出典データセット
uspto-grants-2014_07
特許番号
US08765948B2

反応ノート

読み込み中…