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Sodium hydride → 2-[N-tert-butoxycarbonyl-2,2-difluoro-2-(3-butoxyphenyl)-ethylamino]-N,N-dimethylpropanamide

HRID 62593
ノート
印刷プレビュー

反応式

HRID 62593 の反応式
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([F:23])([F:22])[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[CH:27]([CH3:33])[C:28]([N:30]([CH3:32])[CH3:31])=[O:29]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]([CH2:9][C:10]([F:22])([F:23])[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH:12]=1)[CH:27]([CH3:33])[C:28]([N:30]([CH3:32])[CH3:31])=[O:29])=[O:7])([CH3:2])([CH3:4])[CH3:3]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 24758Sodium hydride2 回HCID 112034Propanamide, 2-chloro-N,N-dimethyl-HCID 71153310N-(tert-butoxycarbonyl)-2,2-difluoro-2-(3-butoxyphenyl)ethylamine

生成物 1

HCID 711521052-[N-tert-butoxycarbonyl-2,2-difluoro-2-(3-butoxyphenyl)-ethylamino]-N,N-dimethylpropanamide収率 85.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide
溶媒

反応条件

温度
0 °C

実験手順

75 mg (0.23 mmol) of N-tert-butoxycarbonyl-2,2-difluoro-2-(3-butoxyphenyl)-ethylamine are dissolved in dry DMF (5 mL). The solution is cooled to 0° C. and NaH (6.7 mg; 1.2 eq) is added. The solution is stirred at RT for 10 min, then cooled again to 0° C. and 2-chloro-N,N-dimethylpropanamide (31 mg; 0.23 mmol) are added. After 4 hours a further 1.2 eq of NaH (6.7 mg) are added. The reaction mixture is stirred overnight at RT, then quenched with water, evaporated, the residue taken up with water and EtAc. The organic layer is separated and the water layer extracted three times with EtAc. The combined organic phases are dried over anhydrous Na2SO4, filtered and evaporated. The resulting crude residue is flash-chromatographed (eluant: petroleum ether/EtAc, 9/1 to 8/2). 2-[N-tert-butoxycarbonyl-2,2-difluoro-2-(3-butoxyphenyl)-ethylamino]-N,N-dimethylpropanamide (84 mg; 81%) is obtained as pale yellow oil.

後処理

  1. temperaturecooled again to 0° C.
  2. stirringThe reaction mixture is stirred overnight at RT
  3. customquenched with water
  4. customevaporated
  5. customThe organic layer is separated
  6. extractionthe water layer extracted three times with EtAc
  7. dry with materialThe combined organic phases are dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe resulting crude residue is flash-chromatographed (eluant: petroleum ether/EtAc, 9/1 to 8/2)

出典と根拠

ORDレコード
ord-cd465b4ad4b04391a0de9f1b2ec984f0
出典データセット
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09447029B2

反応ノート

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