4-Chloro-2-methylpyridine → 2-Fluoro-4-(2-methylpyridin-4-yloxy)phenylamine

HRID 221887ノート

反応式

HRID 221887 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].CC(C)([O-])C.[K+].Cl[C:17]1[CH:22]=[CH:21][N:20]=[C:19]([CH3:23])[CH:18]=1>CC(N(C)C)=O>[F:9][C:3]1[CH:4]=[C:5]([O:8][C:17]2[CH:22]=[CH:21][N:20]=[C:19]([CH3:23])[CH:18]=2)[CH:6]=[CH:7][C:2]=1[NH2:1]

参加物

5

反応物 3

HCID 5813924-Chloro-2-methylpyridineHCID 27359194-Amino-3-fluorophenolHCID 23665647Potassium tert-butoxide

生成物 1

HCID 595579602-Fluoro-4-(2-methylpyridin-4-yloxy)phenylamine収率 47.3%

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒2 回

実験手順

A solution of 4-amino-3-fluorophenol (5.00 g, 39.3 mmol) in anhydrous DMA (100 mL) was treated with potassium tert-butoxide (5.30 g, 47.2 mmol), and the red-brown mixture was stirred at room temperature for 1 h. The mixture was treated with a solution of 4-chloro-2-picoline (5.02 g, 39.3 mmol) in anhydrous DMA (75 mL) and then heated at 100° C. for 17 h. The mixture was cooled to ambient temperature and partitioned between EtOAc (500 mL) and saturated NaCl solution (500 mL). The aqueous phase was back-extracted with EtOAc (300 mL). The combined organic phases were washed with brine, dried over Na2SO4, and concentrated at reduced pressure. Purification through a silica gel plug, eluting with 40% EtOAc/hexane, followed by crystallization from DCM/hexane afforded 4.06 g (47%) of the title compound as a yellow solid. 1H-NMR (DMSO-d6) δ 8.24 (d, J=5.4 Hz, 1H), 6.91 (dd, J=12.3, 2.7 Hz, 1H), 6.80 (dd, J=9.6, 8.7 Hz, 1H), 6.72 to 6.62 (m, 3H), 5.15 (broad s, 2H), (2.36 (s, 3H); MS LC-MS [M+H]+=219, RT=0.24 min.

後処理

  1. temperatureheated at 100° C. for 17 h
  2. temperatureThe mixture was cooled to ambient temperature
  3. custompartitioned between EtOAc (500 mL) and saturated NaCl solution (500 mL)
  4. extractionThe aqueous phase was back-extracted with EtOAc (300 mL)
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated at reduced pressure
  8. customPurification through a silica gel plug
  9. washeluting with 40% EtOAc/hexane
  10. customfollowed by crystallization from DCM/hexane

出典と根拠

ORDレコード
ord-38e4b247f59b4dbdbab866525d5b44ae
出典データセット
uspto-grants-2012_06
特許番号
US08207166B2

反応ノート

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