Dimethyl Sulfone → 1-(4-Difluoromethoxy-3-ethoxy-phenyl)-2-methanesulfonyl-ethylamine

HRID 1694272ノート

反応式

HRID 1694272 の反応式
C1COCC1.[F:6][CH:7]([F:20])[O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=O)=[CH:11][C:10]=1[O:17][CH2:18][CH3:19].[Li][N:22]([Si](C)(C)C)[Si](C)(C)C.[CH3:31][S:32]([CH3:35])(=[O:34])=[O:33]>CO>[F:6][CH:7]([F:20])[O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]([NH2:22])[CH2:31][S:32]([CH3:35])(=[O:34])=[O:33])=[CH:11][C:10]=1[O:17][CH2:18][CH3:19]

参加物

6

反応物 4

HCID 6213Dimethyl SulfoneHCID 8028Tetrahydrofuran2 回HCID 6932854-(Difluoromethoxy)-3-ethoxybenzaldehydeHCID 178418261HCID 178418261、化合物2 回

生成物 1

HCID 588000791-(4-Difluoromethoxy-3-ethoxy-phenyl)-2-methanesulfonyl-ethylamine収率 10%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

To the THF solution (100 ml) of 4-difluoromethoxy-3-ethoxy-benzaldehyde (21.0 g, 0.1 mol) was added dropwise LiN(TMS)2 (1M in THF, 100 ml, 0.1 mol) at 0° C. After 15 minutes of stirring, BF3 THF complex (22 ml, 0.2 mol) was added to the reaction mixture (1). To the THF solution (100 ml) of methyl sulfone (9.4 g, 0.1 mol) was added LiN(TMS)2 (1M in THF, 100 ml, 0.1 mol) at −78° C. The mixture (2) was stirred at −78° C. for 1 hour. Mixture (1) was added to the mixture (2) via a 2-way needle. The mixture was allowed to warm to room temperature and stirred at room temperature for 18 hours. MeOH (20 ml) was added to quench the reaction. The mixture was concentrated in vacuo until there was one-fourth left. To the resulted mixture was added HCl aqueous solution (20%, 150 ml) followed by concentrated HCl until pH=3. The mixture was extracted with ether (100 ml×3). The aqueous layer was neutralized with NaOH (15 M) till pH=8. The mixture was extracted with methylene chloride (100 ml×3). The combined organic layer was washed with water (100 ml×2), brine (100 ml), dried over Na2SO4 and concentrated in vacuo. The resulted oil was purified by silica gel column to give 1-(4-difluoromethoxy-3-ethoxy-phenyl)-2-methanesulfonyl-ethylamine (2.8 g, 10%) as yellow oil. 1H NMR (CDCl3) δ 1.41 (t, J=6.8 Hz, 3H, OCH2CH3), 3.30-3.40 (m, 2H, CH2SO2), 3.45 (s, 3H, CH3), 4.58-4.64 (m, 1H, CHN), 6.53 (t, J=75 Hz, 1H, CF2H), 6.84-7.12 (m, 3H, Ar).

後処理

  1. stirringstirred at room temperature for 18 hours
  2. customto quench
  3. customthe reaction
  4. concentrationThe mixture was concentrated in vacuo until there
  5. additionTo the resulted mixture was added HCl aqueous solution (20%, 150 ml)
  6. extractionThe mixture was extracted with ether (100 ml×3)
  7. extractionThe mixture was extracted with methylene chloride (100 ml×3)
  8. washThe combined organic layer was washed with water (100 ml×2), brine (100 ml)
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo
  11. customThe resulted oil was purified by silica gel column

出典と根拠

ORDレコード
ord-06060bb0b7a548778bc3224e61c70e34
出典データセット
uspto-grants-2012_04
特許番号
US08158672B2

反応ノート

読み込み中…