Potassium Phosphate, Tribasic → tert-Butyl 4-(4-cyclopropyl-1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate

HRID 2088884ノート

反応式

HRID 2088884 の反応式
Br[C:2]1[N:3]=[C:4]([CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[N:5]([CH2:7][CH2:8][O:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][O:11]2)[CH:6]=1.[CH:29]1(B(O)O)[CH2:31][CH2:30]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:29]1([C:2]2[N:3]=[C:4]([CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)[N:5]([CH2:7][CH2:8][O:9][CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][O:11]3)[CH:6]=2)[CH2:31][CH2:30]1

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 67265112tert-Butyl 4-(4-bromo-1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate

生成物 1

HCID 67968740tert-Butyl 4-(4-cyclopropyl-1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate収率 37%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒2 回HCID 1140Toluene溶媒

実験手順

Add tert-butyl 4-(4-bromo-1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate (1.82 g, 3.97 mmol), cyclopropylboronic acid (0.44 g, 1.3 eq), tricyclohexylphosphine (0.11 g, 0.1 eq), and potassium phosphate (2.95 g, 3.5 eq) in toluene (18 mL) and water (0.9 mL). Degas with nitrogen for 5 minutes. Add palladium acetate (0.045 g, 0.05 eq) and heat at 90° C. overnight. Stop heating after 12 hrs. Dilute with water then extract with ethyl acetate three times. Dry over anhydrous magnesium sulfate and concentrate in vacuo. Purify by silica gel chromatography, eluting with 0-20-50% ethyl acetate/hexanes, then with 1-3-5-7% methanol/dichloromethane, to give the title compound (0.61 g, 37%). MS (ES) m/z=420 [M]+.

後処理

  1. customDegas with nitrogen for 5 minutes
  2. temperatureStop heating after 12 hrs
  3. extractionthen extract with ethyl acetate three times
  4. dry with materialDry over anhydrous magnesium sulfate
  5. concentrationconcentrate in vacuo
  6. customPurify by silica gel chromatography
  7. washeluting with 0-20-50% ethyl acetate/hexanes

出典と根拠

ORDレコード
ord-b0276ffa2b1b4c7791fab89acf5d0a82
出典データセット
uspto-grants-2013_05
特許番号
US08436002B2

反応ノート

読み込み中…