Nitrogen → Methyl 3-amino-2-fluorobenzoate

HRID 239248

反応式

HRID 239248 の反応式
C(=O)(OC(C)(C)C)[NH2:2].Br[C:10]1[C:11]([F:20])=[C:12]([CH:17]=[CH:18][CH:19]=1)[C:13]([O:15][CH3:16])=[O:14].C(Cl)(Cl)Cl.C(=O)([O-])[O-].[Cs+].[Cs+].N#N.C(O)(C(F)(F)F)=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].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C1(C)C=CC=CC=1>[NH2:2][C:10]1[C:11]([F:20])=[C:12]([CH:17]=[CH:18][CH:19]=1)[C:13]([O:15][CH3:16])=[O:14]

参加物

10

反応物 6

HCID 947NitrogenHCID 6212ChloroformHCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 21584505Methyl 3-bromo-2-fluorobenzoate

生成物 1

HCID 46311080Methyl 3-amino-2-fluorobenzoate収率 76.2%

試薬・触媒・溶媒 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
90 °C

実験手順

In a 500 mL flask was placed 1,1-dimethylethyl carbamate (6.03 g, 51.5 mmol), methyl 3-bromo-2-fluorobenzoate (10 g, 42.9 mmol), Pd2(dba)3.CHCl3 (0.89 g, 0.86 mmol), xantphos (1.49 g, 2.57 mmol) and cesium carbonate (16.8 g, 51.5 mmol). The flask was sealed with a rubber septum, placed under high vacuum, and toluene (200 mL) was added. Three cycles of high vacuum/N2 were performed and the reaction mixture was stirred at 90° C. overnight. The reaction was filtered through a pad of celite with EtOAc washing and concentrated. To the residue was added DCM (200 mL) followed by TFA (50 mL, 649 mmol), and the mixture was stirred at rt for 1 h. The volatiles were removed under reduced pressure and the residue was taken up in EtOAc and washed with saturated NaHCO3 and brine. The organic layer was dried over NaSO4, stripped onto silica and column chromatographed on silica with 5% to 50% EtOAc:Hexane to give 5.53 g (76%) of the title compound of Step B. 1H-NMR (400 MHz, DMSO-d6) δ 6.92-7.01 (m, 3H), 5.37 (s, 2H), and 3.81 (s, 3H). MS (ESI): 170 [M+H]+.

後処理

  1. customIn a 500 mL flask was placed
  2. customThe flask was sealed with a rubber septum
  3. additionwas added
  4. filtrationThe reaction was filtered through a pad of celite with EtOAc washing
  5. concentrationconcentrated
  6. additionTo the residue was added DCM (200 mL)
  7. stirringthe mixture was stirred at rt for 1 h
  8. customThe volatiles were removed under reduced pressure
  9. washwashed with saturated NaHCO3 and brine
  10. dry with materialThe organic layer was dried over NaSO4
  11. customchromatographed on silica with 5% to 50% EtOAc

出典と根拠

ORDレコード
ord-d7c2abed2d7847de99c1a709d3358aa8
出典データセット
uspto-grants-2014_02
特許番号
US08642759B2

関連ノート

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