Trifluoroacetic acid → HCID 60104786, compound

HRID 895693Notes

Reaction equation

HRID 895693 reaction equation
FC(F)(F)C(O)=O.C([O:12][C:13](=[O:33])[C@@H:14]([N:16]1[CH2:25][CH2:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]1[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[CH3:32])[CH3:15])(C)(C)C>ClCCl>[C:27]1([CH3:32])[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[C@@H:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:24][CH2:25][N:16]1[C@@H:14]([CH3:15])[C:13]([OH:33])=[O:12].[C:27]1([CH3:32])[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[C@H:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:24][CH2:25][N:16]1[C@@H:14]([CH3:15])[C:13]([OH:33])=[O:12]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 60104788HCID 60104788, compound

Product 2

HCID 60104786HCID 60104786, compoundHCID 60104795HCID 60104795, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (5.0 mL, 64.9 mmol) is added to a solution of 2-(S)-(1-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl)-propionic acid tert-butyl ester (0.27 g, 0.768 mmol) in dichloromethane (5.0 mL). The reaction mixture is stirred at room temperature for 4 hours. All solvent is removed in vacuo, ethyl ether (50 mL) and saturated sodium bicarbonate (100 mL) are added and the organic layer is removed. The aqueous layer is acidified to pH 2.0 using 1M HCl and the crude product extracted into dichloromethane (100 mL), washed with water (2×50 mL) and brine (1×100 mL), and dried over magnesium sulfate. Filtration and concentration are followed by flash chromatography on SiO2 using 20:1 dichloromethane:methanol and afford 100 mg 2-(S)-[1-(R)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid (Rf of 0.6) and 70 mg 2-(S)-[1-(S)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid (Rf of 0.3) both as white foams. 2-(S)-[1-(R)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid, 2-(R)-[1-(S)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid and 2-(R)-[1-(R)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionic acid are prepared in similar fashion. D. N-(2-fluoro-benzyl)-N-indan-2-yl-2-(S)-[1-(S)-o-tolyl-3,4-dihydro-1H-isoquinolin-2-yl]-propionamide (Compound 9)

Workup

  1. customAll solvent is removed in vacuo, ethyl ether (50 mL) and saturated sodium bicarbonate (100 mL)
  2. additionare added
  3. customthe organic layer is removed
  4. extractionthe crude product extracted into dichloromethane (100 mL)
  5. washwashed with water (2×50 mL) and brine (1×100 mL)
  6. dry with materialdried over magnesium sulfate
  7. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-084966c3044d43a78e5777e5de3a6b94
Source dataset
uspto-grants-2005_07
Patent number
US06916830B2

Reaction notes

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