Trifluoroacetic acid → (2R)-N-(2-(2-(3-hydroxypropoxy)phenyl)ethyl)-N-methyl-2-(methylamino)-3-(2-naphthyl)propionamide

HRID 650837Notes

Reaction equation

HRID 650837 reaction equation
C(O[C:6](=O)[N:7]([C@@H:9]([C:21](=[O:37])[N:22]([CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[O:32][CH2:33][CH2:34][CH2:35][OH:36])[CH3:23])[CH2:10][C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=1)C)(C)(C)C.FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+]>ClCCl>[OH:36][CH2:35][CH2:34][CH2:33][O:32][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[CH2:25][CH2:24][N:22]([CH3:23])[C:21](=[O:37])[C@H:9]([NH:7][CH3:6])[CH2:10][C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium Bicarbonate2×HCID 54458179N-[(1R)-1-(N-{2-[2-(3-hydroxypropoxy)phenyl]ethyl}-N-methylcarbamoyl)-2-(2-naphthyl)ethyl]-N-methylcarbamic acid tert-butyl ester

Product 1

HCID 10645806(2R)-N-(2-(2-(3-hydroxypropoxy)phenyl)ethyl)-N-methyl-2-(methylamino)-3-(2-naphthyl)propionamideYield 69.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of N-[(1R)-1-(N-{2-[2-(3-hydroxypropoxy)phenyl]ethyl}-N-methylcarbamoyl)-2-(2-naphthyl)ethyl]-N-methylcarbamic acid tert-butyl ester (383 mg, 0.74 mmol) in dichloromethane (4 ml) was cooled to 0° C. Trifluoroacetic acid (4 ml) was added. The reaction mixture was stirred for 105 min at 0° C. Dichioromethane (40 ml) was added. A saturated aqueous solution of sodium hydrogen carbonate (40 ml) was added dropwise. Solid sodium hydrogen carbonate was added, until pH 7 was obtained. The phases were separated. The aqueous phase was extracted with dichloromethane (3×60 ml). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (30 g), using dichloromethane/methanol/25% aqueous ammonia (100:10:1) as eluent, to give 216 mg of (2R)-N-(2-(2-(3-hydroxypropoxy)phenyl)ethyl)-N-methyl-2-(methylamino)-3-(2-naphthyl)propionamide.

Workup

  1. customwas obtained
  2. customThe phases were separated
  3. extractionThe aqueous phase was extracted with dichloromethane (3×60 ml)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. customThe solvent was removed in vacuo
  6. customThe crude product was purified by flash chromatography on silica (30 g)

Sources & evidence

ORD record
ord-608e0b9ce95e4bc08cd27059f739d0f7
Source dataset
uspto-grants-2001_08
Patent number
US06274584B1

Reaction notes

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