Hydrochloric Acid → 2-[2,2-difluoro-2-(3-butoxyphenyl)-ethylamino]-N,N-dimethylpropanamide

HRID 62594Notes

Reaction equation

HRID 62594 reaction equation
C(OC([N:8]([CH2:16][C:17]([F:30])([F:29])[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH:19]=1)[CH:9]([CH3:15])[C:10]([N:12]([CH3:14])[CH3:13])=[O:11])=O)(C)(C)C.Cl>C(Cl)Cl.O1CCOCC1>[F:29][C:17]([F:30])([C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH:19]=1)[CH2:16][NH:8][CH:9]([CH3:15])[C:10]([N:12]([CH3:14])[CH3:13])=[O:11]

Participants

5

Reactant 2

HCID 313Hydrochloric Acid3×HCID 711521052-[N-tert-butoxycarbonyl-2,2-difluoro-2-(3-butoxyphenyl)-ethylamino]-N,N-dimethylpropanamide

Product 1

HCID 711520482-[2,2-difluoro-2-(3-butoxyphenyl)-ethylamino]-N,N-dimethylpropanamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

84 mg (0.196 mmol) of 2-[N-tert-butoxycarbonyl-2,2-difluoro-2-(3-butoxyphenyl)-ethylamino]-N,N-dimethylpropanamide are dissolved in 3 mL of DCM and 0.49 mL (1.96 mmmol; 10 eq) of a 4M HCl solution in dioxane are added. After 8 hours, further 10 eq (0.49 mL) of 4M HCl 1 dioxane are added and the mixture is stirred overnight. Further 5 eq (0.245 mL) of 4M HCl in dioxane are the added and the mixture stirred for further 24 hours. The solution is evaporated, the white residue suspended in diethyl ether and then evaporated twice. The residue is flash-chromatographed on silica gel (DCM/MeOH 1/1 as an eluant followed by MeOH/conc. NH3 95/5). and the free base 2-[2,2-difluoro-2-(3-butoxyphenyl)-ethylamino]-N,N-dimethylpropanamide is isolated as a pale yellow fluid. The compound is dissolved in DCM (3 mL) and 4M HCl in dioxane is added to bring the solution to pH 2. The mixture is stirred for 10 minutes and then evaporated. The white residue is taken up with ether and evaporated twice. 45 mg (49%) of 2-[2,2-difluoro-2-(3-butoxyphenyl)-ethylamino]-N,N-dimethylpropanamide, hydrochloride (Example 2-1) are obtained.

Workup

  1. additionadded
  2. stirringthe mixture stirred for further 24 hours
  3. customThe solution is evaporated
  4. customevaporated twice
  5. customThe residue is flash-chromatographed on silica gel (DCM/MeOH 1/1 as an eluant

Sources & evidence

ORD record
ord-5496ee86950444659b30daa10c447879
Source dataset
uspto-grants-2016_09
Patent number
US09447029B2

Reaction notes

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