1-Phenethylamine, (-)- → (s)-6-Chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylic acid

HRID 1636673Notes

Reaction equation

HRID 1636673 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([OH:18])=[O:17])=[CH:5]2.C[C@H](N)C1C=CC=CC=1>C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C@H:7]([C:12]([F:15])([F:13])[F:14])[C:6]([C:16]([OH:18])=[O:17])=[CH:5]2

Participants

4

Reactant 2

HCID 758181-Phenethylamine, (-)-HCID 100163706-Chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylic acid

Product 1

HCID 9878729(s)-6-Chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylic acid

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylic acid (Example 157)(6.75 g, 24.3 mmol) in ethyl acetate (25 mL) was added (S)-(-)-α-methylbenzylamine (1.50 g, 12.2 mmol). To the resulting solution was added hexanes (50 mL) with mixing. Stirring was discontinued and the reaction held static at room temperature for 16 hours during which time yellow crystals formed. The crystals were collected and washed with ethyl acetate-hexanes (100 mL, 1:2). The resulting yellow solid (932 mg) was dissolved in ethyl acetate (20 mL) and extracted with 1 N HCl (3×10 mL). The organic layer was dried over sodium sulfate and solvent removed at reduced pressure. The (s)-6-chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylic acid was obtained as a yellow solid (648 mg, 10% yield). mp 173-176° C. 1H NMR (acetone-d6, 300 MHz) 7.80 (s, 1H), 7.35(d, 1H, J=2.2 Hz), 7.18 (d, 1H, J=8.0, J=2.2 Hz), 6.86 (d, 1H, J=8.0 Hz), 6.60 (brs, 1H), 5.20 (m, 1H). Anal. Calc'd. for C11H7NO2F3Cl C, 47.40 H, 2.54; N, 5.40. Found C, 47.49; H, 2.60; N, 4.98. The compound was determined to have an optical purity greater than 90% ee. Optical purity was determined by HPLC as described in Example 66.

Workup

  1. additionwith mixing
  2. customformed
  3. customThe crystals were collected
  4. washwashed with ethyl acetate-hexanes (100 mL, 1:2)
  5. dissolutionThe resulting yellow solid (932 mg) was dissolved in ethyl acetate (20 mL)
  6. extractionextracted with 1 N HCl (3×10 mL)
  7. dry with materialThe organic layer was dried over sodium sulfate and solvent
  8. customremoved at reduced pressure

Sources & evidence

ORD record
ord-403dceb62dab449f942e725b205219f6
Source dataset
uspto-grants-2000_03
Patent number
US06034256

Reaction notes

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