Acetic Acid → HCID 86650663, compound

HRID 1969465Notes

Reaction equation

HRID 1969465 reaction equation
[F:1][C:2]([F:7])([F:6])C(O)=O.[C:8]1([C@@H:14]2[NH:18][C:17](=[O:19])[CH:16]=[CH:15]2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH3:20][C:21]([OH:23])=O.[CH3:24][C:25]([NH2:37])([C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[N:28]=1)[CH3:26]>C1(C)C=CC=CC=1.O>[CH3:26][C:25]([NH:37][C:16]1[C:17](=[O:19])[N:18]([C:8]2[CH:13]=[CH:20][C:21]([O:23][C:2]([F:7])([F:6])[F:1])=[CH:10][CH:9]=2)[C@@H:14]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:15]=1)([C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:35])([F:36])[F:34])[N:28]=1)[CH3:24]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 573469902-[6-(Trifluoromethyl)pyridin-2-yl]propan-2-amineHCID 86650661HCID 86650661, compound

Product 1

HCID 86650663HCID 86650663, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 1140TolueneSolvent

Procedure

Add water (490 mL) and trifluoroacetic acid (126 mL, 1.67 mol) sequentially to a solution of 1-(4-trifluoromethoxy-phenyl)-3-(R)-1-phenyl-ethylamino)-5(R)-phenyl-1,5-dihydro-pyrrol-2-one (245 g, 558 mmol) in toluene (1.22 L). Stir at ambient temperature for 2 hours. Add water (1.0 L) and discard the aqueous layer. Wash the organic layer with 1N HCl (500 mL×2). To the organic layer add HOAc (10 mL, 174 mmol) and 1-methyl-1-(6-trifluoromethyl-pyridin-2-yl)-ethylamine (170 g, 836 mmol). Heat to 40° C. for 18 hours. Add water (400 mL), separate and discard the aqueous layer. Wash the organic layer with water (500 mL) and concentrate the organic layer to a dark oil. Dissolve the residue in toluene (400 mL) and concentrate to a brown paste. Triturate the solid with 20% MTBE/hexanes (1.0 L). Filter the mixture and collect the title compound as white solid (190 g, 65%). 1H NMR (400 MHz, DMSO-d6) δ 8.01 (m, 1H), 7.83 (d, J=8 Hz, 1H), 7.69 (d, J=8 Hz, 1H), 7.64 (d, 12 Hz, 2H), 7.26 (d, J=8 Hz, 2H), 7.17 (m, 3H), 7.03 (d, J=8 Hz, 2H), 5.78 (s, 1H), 5.73 (s, 1H), 4.70 (s, 1H), 1.62 (s, 3H), 1.59 (s, 3H) LC-MS ESI m/z: 522 (M+H)+, Tr=6.53 min., method 1.

Workup

  1. washWash the organic layer with 1N HCl (500 mL×2)
  2. temperatureHeat to 40° C. for 18 hours
  3. customAdd water (400 mL), separate
  4. washWash the organic layer with water (500 mL)
  5. concentrationconcentrate the organic layer to a dark oil
  6. dissolutionDissolve the residue in toluene (400 mL)
  7. concentrationconcentrate to a brown paste
  8. customTriturate the solid with 20% MTBE/hexanes (1.0 L)
  9. filtrationFilter the mixture
  10. customcollect the title compound as white solid (190 g, 65%)
  11. custom522 (M+H)+, Tr=6.53 min., method 1

Sources & evidence

ORD record
ord-a8ff72b0946c4803aa8fe23676404bd6
Source dataset
uspto-grants-2013_04
Patent number
US08426448B2

Reaction notes

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