Hydrochloric Acid → (2-Amino-5-chlorophenyl)(pyridin-2-yl)methanone

HRID 29506

反応式

HRID 29506 の反応式
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])CCC.[NH2:13][C:14]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:15]=1[C:16](O)=[O:17].Cl[Si](C)(C)C.Cl>CCOCC.C1COCC1>[NH2:13][C:14]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:15]=1[C:16]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1)=[O:17]

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 6397ChlorotrimethylsilaneHCID 79732-BromopyridineHCID 124762-Amino-5-chlorobenzoic acidHCID 178418339Butyllithium

生成物 1

HCID 288049(2-Amino-5-chlorophenyl)(pyridin-2-yl)methanone収率 45.1%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 2-bromopyridine (5 ml, 52 mmol) in Et2O (60 ml) was added 40 ml of a n-butyllithium (1.6M in hexane, 64 mmol) drop wise at −40° C. over 30 min under a nitrogen atmosphere. The resulting yellow solution was stirred for a further 1 hr at −50° C. to −30° C. In a separate flask, a solution of 2-amino-5-chlorobenzoic acid (2.05 g, 12 mmol) in dry THF (90 ml), under nitrogen atmosphere and with ice-cooling, was added in one portion to the solution prepared as described above. The reaction mixture was stirred for 2 hrs at 0° C. and then chlorotrimethylsilane (30 ml) was added at 0° C. with stirring. The reaction mixture was allowed to warm to room temperature and 1 N HCl aq (100 ml) was added. The resulting two-phase system was separated. The aqueous phase was adjusted to pH12 with 6N NaOH solution and extracted with ethyl acetate (2×150 ml). The combined organic extractions were dried over Na2SO4. After removal of solvent, the residue was purified by the flash chromatography using ethyl acetate/hexane (1:4) as eluent. Crystallization of the product from Et2O/hexane mixture gave 1.26 g (45%) of desired product as yellow solid. 1H-NMR (DMSO-d6, 500 MHz): δ 6.90 (1H, d, J=9 Hz), 7.31 (1H, dd, J=9 and 2.5 Hz), 7.40 (2H, br), 7.53 (1H, d, J=2.5 Hz), 7.61 (1H, m), 7.79 (1H, d, J=8 Hz), 8.03 (1H, m), 8.69 (1H, m). MS: (ESI+): 233.2 (M+1).

後処理

  1. additionwas added in one portion to the solution
  2. customprepared
  3. stirringThe reaction mixture was stirred for 2 hrs at 0° C.
  4. stirringwith stirring
  5. customThe resulting two-phase system was separated
  6. extractionextracted with ethyl acetate (2×150 ml)
  7. extractionThe combined organic extractions
  8. dry with materialwere dried over Na2SO4
  9. customAfter removal of solvent
  10. customthe residue was purified by the flash chromatography
  11. customCrystallization of the product from Et2O/hexane mixture

出典と根拠

ORDレコード
ord-7505e72185284a5d9da00d99b64cd23e
出典データセット
uspto-grants-2008_09
特許番号
US07420055B2

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