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

HRID 62593
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HRID 62593 반응식
[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]
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참가 물질

5

반응물 3

HCID 24758Sodium hydride2회HCID 112034Propanamide, 2-chloro-N,N-dimethyl-HCID 71153310N-(tert-butoxycarbonyl)-2,2-difluoro-2-(3-butoxyphenyl)ethylamine

생성물 1

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

시약·촉매·용매 1

HCID 6228
Dimethylformamide
용매

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온도
0 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-cd465b4ad4b04391a0de9f1b2ec984f0
출처 데이터셋
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09447029B2

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