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

HRID 62593Notes

Reaction equation

HRID 62593 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-cd465b4ad4b04391a0de9f1b2ec984f0
Source dataset
uspto-grants-2016_09
Patent number
US09447029B2

Reaction notes

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