Potassium Phosphate, Tribasic → (3,5-Dimethyl-3'-trifluoromethoxy-biphenyl-4-yl)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

HRID 1692394ノート

反応式

HRID 1692394 の反応式
Br[C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([C:9]([N:11]2[CH2:16][CH2:15][CH:14]([N:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[CH2:13][CH2:12]2)=[O:10])=[C:4]([CH3:22])[CH:3]=1.[F:23][C:24]([F:36])([F:35])[O:25][C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.[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>[CH3:22][C:4]1[CH:3]=[C:2]([C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([O:25][C:24]([F:23])([F:35])[F:36])[CH:27]=2)[CH:7]=[C:6]([CH3:8])[C:5]=1[C:9]([N:11]1[CH2:16][CH2:15][CH:14]([N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[CH2:13][CH2:12]1)=[O:10]

参加物

6

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 66901599(4-Bromo-2,6-dimethyl-phenyl)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone2 回

生成物 1

HCID 25190014(3,5-Dimethyl-3'-trifluoromethoxy-biphenyl-4-yl)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone収率 77%

試薬・触媒・溶媒 2

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

To a degassed solution of 0.130 g (0.35 mmol) of (4-bromo-2,6-dimethyl-phenyl)-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (intermediate 1) and 0.147 g (0.70 mmol) of 3-trifluoromethoxy-phenyl boronic acid in 5 ml of DMF was added 2.50 ml of tribasic potassium phosphate solution (2M in water) drop by drop, followed by 0.022 g (0.019 mmol) of tetrakis-(triphenylphosphine)-palladium. This reaction mixture was stirred at 80° C. for two hours and subsequently cooled down to RT, then poured into crashed ice and extracted three times with CH2Cl2; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 95:5) to give 0.12 g (77%) of the title compound as light yellow amorphous solid. MS: 447.2 (MH+).

後処理

  1. temperaturesubsequently cooled down to RT
  2. additionpoured
  3. extractionextracted three times with CH2Cl2
  4. washthe organic phases were washed with water
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 95:5)

出典と根拠

ORDレコード
ord-a470e3353d50409e8ad58284493018a9
出典データセット
uspto-grants-2012_04
特許番号
US08153805B2

反応ノート

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