Oxalic Acid → (E)-5-(2-(4-fluorophenyl)prop-1-enyl)-2-methyl-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1401548ノート

反応式

HRID 1401548 の反応式
[CH3:1][N:2]1[CH2:18][CH2:17][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.N1CCC[C@H]1C(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[CH:36]=[C:37]([C:39]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=1)[CH3:38].C(O)(=O)C(O)=O>CN(C=O)C.C1COCC1.[Cu]I>[F:45][C:42]1[CH:43]=[CH:44][C:39](/[C:37](/[CH3:38])=[CH:36]/[N:6]2[C:7]3[CH:8]=[CH:9][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11][C:12]=3[C:4]3[CH2:3][N:2]([CH3:1])[CH2:18][CH2:17][C:5]2=3)=[CH:40][CH:41]=1

参加物

9

反応物 5

HCID 971Oxalic AcidHCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 67311103HCID 67311103、化合物HCID 86644757(1-Bromoprop-1-en-2-yl)-4-fluorobenzene

生成物 1

HCID 59455160(E)-5-(2-(4-fluorophenyl)prop-1-enyl)-2-methyl-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

2-Methyl-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (127 mg, 0.5 mmol) was dissolved in DMF. Copper (I) iodide (9.5 mg, 0.05 mmol), L-proline (11.5 mg, 0.1 mmol) and potassium phosphate (212 mg, 1 mmol) were added and the reaction mixture was stirred for 10 min. at RT. 1-(1-Bromoprop-1-en-2-yl)-4-fluorobenzene (118 mg, 0.55 mmol) was added dropwise and the reaction mixture was purged with nitrogen. The reaction mixture was heated overnight at 90° C. (prolonged heating in some cases was required). DMF was evaporated under reduced pressure, the residue was diluted with water and the solid was filtered. The solid material was purified by silica gel chromatography (100-200 mesh) eluting with 0-3% MeOH-DCM. The free base was converted into oxalate salt by treatment of oxalic acid (1 equiv) in THF. Yield: 65 mg as the oxalate salt. 1H NMR (CD3OD, oxalate salt) δ (ppm): 7.90 (s, 1H), 7.70 (t, 2H), 7.50 (d, 1H), 7.40 (d, 1H), 7.20 (t, 2H), 7.0 (s, 1H), 4.60 (m, 2H), 3.78 (m, 2H), 3.20 (m, 2H), 3.10 (s, 3H), 1.90 (s, 3H).

後処理

  1. customthe reaction mixture was purged with nitrogen
  2. temperatureThe reaction mixture was heated overnight at 90° C. (
  3. temperatureprolonged heating in some cases
  4. customDMF was evaporated under reduced pressure
  5. additionthe residue was diluted with water
  6. filtrationthe solid was filtered
  7. customThe solid material was purified by silica gel chromatography (100-200 mesh)
  8. washeluting with 0-3% MeOH-DCM

出典と根拠

ORDレコード
ord-b9e506ce284249569e73f96bb75b6ee5
出典データセット
uspto-grants-2014_12
特許番号
US08907097B2

反応ノート

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