Triethylamine → Methyl 4-chloro-2-(3-pyridyl)acetamidobenzoate

HRID 326282ノート

反応式

HRID 326282 の反応式
[NH2:1][C:2]1[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].Cl.[N:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1CC(O)=O.C(N(CC)CC)C.O=C1N(P(Cl)(N2CCOC2=O)=O)[CH2:35][CH2:34][O:33]1.N1C=CC=CC=1CC(O)=O>ClCCCl>[Cl:12][C:10]1[CH:9]=[CH:8][C:3]([C:4]([O:6][CH3:7])=[O:5])=[C:2]([NH:1][C:34](=[O:33])[CH2:35][C:18]2[CH:19]=[N:14][CH:15]=[CH:16][CH:17]=2)[CH:11]=1

参加物

7

反応物 5

HCID 8471Triethylamine2 回HCID 80001Methyl 4-chloroanthranilateHCID 853172-Pyridineacetic acid, hydrochloride (1:1)HCID 853182-Pyridineacetic acidHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chloride

生成物 1

HCID 19736673Methyl 4-chloro-2-(3-pyridyl)acetamidobenzoate

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

実験手順

To a solution of methyl 2-amino-4-chlorobenzoate (2 g, 10.8 mmol) in 1,2-dichlorethane (60 ml) was added 2-pyridylacetic acid hydrochloride (1.9 g, 10.8 mmol), triethylamine (3.2 ml, 22.7 mmol) and bis (2-oxo-3-oxazolidinyl)phosphinic chloride and the reaction refluxed for 8 h. More 2-pyridylacetic acid (1.9 g, 10.8 mmol) and triethylamine (3.2 ml, 22.7 mmol) were added and refluxing continued for a further 16 h. The solvent was evaporated and the residue partitioned between saturated aqueous sodium bicarbonate solution (50 ml) and dichloromethane (50 ml). The organic phase was dried (MgSO4) and evaporated. The residue was purified by flash chromatography on silica (eluting with 50% ethyl acetate/60°-90° petrol) to afford methyl 4-chloro-2-(3-pyridyl)acetamidobenzoate as a green solid (2.5 g), m.p. 85°-87° C. To a solution of the foregoing amide (1 g, 3.3 mmol) in tetrahydrofuran (40 mml) was added a solution of potassium hexamethyldisilazide in toluene (0.5M, 16.6 ml, 8.3 mmol) and the reaction stirred for 2 h. Methanol (15 ml) was added and the solvent evaporated. The residue was partitioned between aqueous sodium hydroxide (1M, 40 ml) and diethyl ether (40 ml), and the aqueous layer acidified with hydrochloric acid (5M). The resultant precipitate was collected and recrystallised from dimethylformamide/water to afford the title compound as a yellow-green solid; m.p.>330° C. (from DMF/H2O) (Found: C, 61.48; H, 3.20; N, 10.20; C14H9ClN2O2 requires C, 61.66; H, 3.33; N, 10.27%); δH (DMSO-d6) 7.15 (1H, dd, J=8.5 Hz and 1.9 Hz, 5-H), 7.26 (1H, s, 8-H), 7.42 (1H, t, J=6.1 Hz, 5'-H), 8.02 (1H, d, J=8.5 Hz, 5-H), 8.16 (1H, t, J=7.3 Hz, 4'-H), 8.78 (1H, d, J=8.6 Hz, 6'-H), 9.38 (1H, d, J=8.8 Hz, 3'-H), 11.20 (1H, s, NH); m/z 272 (M+).

後処理

  1. temperaturethe reaction refluxed for 8 h
  2. temperaturerefluxing
  3. customThe solvent was evaporated
  4. customthe residue partitioned between saturated aqueous sodium bicarbonate solution (50 ml) and dichloromethane (50 ml)
  5. dry with materialThe organic phase was dried (MgSO4)
  6. customevaporated
  7. customThe residue was purified by flash chromatography on silica (eluting with 50% ethyl acetate/60°-90° petrol)

出典と根拠

ORDレコード
ord-c2682c8eec7843e69178a774e2b5f3fc
出典データセット
uspto-grants-1993_12
特許番号
US05268378

反応ノート

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