Trifluoroacetic acid → (2R)-1-(1,2,3,4-tetrahydroisoquinolin-2-yl)-2-(methylamino)-3-(2-naphthyl)-1-propanone

HRID 366123Notes

Reaction equation

HRID 366123 reaction equation
C(O[C:6](=O)[N:7]([C@H:9]([CH2:22][C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=1)[C:10]([N:12]1[CH2:21][CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:13]1)=[O:11])C)(C)(C)C.FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+]>ClCCl>[CH2:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:20][CH2:21][N:12]1[C:10](=[O:11])[C@H:9]([NH:7][CH3:6])[CH2:22][C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium Bicarbonate2×HCID 54129692N-((1R)-2-(1,2,3,4-Tetrahydroisoquinolin-2-yl)-1-((2-naphthyl)methyl)-2-oxoethyl)-N-methylcarbamic acid tert-butyl ester

Product 1

HCID 10783666(2R)-1-(1,2,3,4-tetrahydroisoquinolin-2-yl)-2-(methylamino)-3-(2-naphthyl)-1-propanoneYield 46.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

N-((1R)-2-(1,2,3,4-Tetrahydroisoquinolin-2-yl)-1-((2-naphthyl)methyl)-2-oxoethyl)-N-methylcarbamic acid tert-butyl ester (6.12 g, 13.8 mmol) was dissolved in dichloromethane (40 ml). The solution was cooled to 0° C. Trifluoroacetic acid (40 ml) was added. The reaction mixture was stirred for 90 min at 0° C. Dichloromethane (110 ml) and a saturated aqueous solution of sodium hydrogen carbonate (150 ml) were added successively. 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 (130 g), using dichloromethane/methanol/25% aqueous ammonia 100:10:1 as eluent, to give 2.20 g of (2R)-1-(1,2,3,4-tetrahydroisoquinolin-2-yl)-2-(methylamino)-3-(2-naphthyl)-1-propanone.

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 (130 g)

Sources & evidence

ORD record
ord-c173d04bc26d44c9b8302df3346f4c10
Source dataset
uspto-grants-2000_10
Patent number
US06127354

Reaction notes

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