Toluene → HCID 11512394, compound

HRID 1993978Notes

Reaction equation

HRID 1993978 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[O:24][CH2:23][C@@H:19]3[CH2:20][NH:21][CH2:22][C@H:18]3[C@@H:17]2[C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[C:34]1(=O)[CH2:38][CH2:37][C:36](=[O:39])[CH2:35]1.CC1C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>CCOC(C)=O>[F:33][C:2]([F:1])([F:32])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[O:24][CH2:23][C@@H:19]3[CH2:20][N:21]([C:34]4[CH2:38][CH2:37][C:36](=[O:39])[CH:35]=4)[CH2:22][C@H:18]3[C@@H:17]2[C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:8]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 6101p-Toluenesulfonic acidHCID 774661,3-CyclopentanedioneHCID 11698610HCID 11698610, compound

Product 1

HCID 11512394HCID 11512394, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

(3aS,6R,7R,7aR)-6-{(1R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethoxy}-7-(4-fluorophenyl)octahydropyrano[3,4-c]pyrrole (example 2: 646 mg, 1.35 mmol) was combined with 1,3-cyclopentanedione (200 mg, 2.03 mmol) and PTSA (26 mg, 0.135 mmol). Toluene (15 mL) was added to the reagents and the vessel was heated to 95° C. for 1 hr. The reaction was diluted with EtOAc and washed twice with 2N NaOH. The aqueous layer was extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered through a fritted funnel and concentrated in vacuo. The crude residue was purified on silica gel and eluted with a 1 to 5% linear gradient of (10% NH4OH-methanol)/DCM which furnished the title compound. 1H-NMR (CD3OD): δ 1.38 (d, 3H, J=7.0 Hz), 2.20-2.44 (m, 4H), 2.55-2.84 (m, 3H), 2.80-3.24 (m, 2H), 3.34-3.80 (m, 3H), 4.24-4.34 (m, 1H), 4.42 (dd, 1H, J=2.5, 8.0 Hz), 4.78-4.92 (m, 1H), 5.09 (q, 1H, J=7.0 Hz), 6.96-7.02 (m, 2H), 7.20 (dd, 2H, J=6.05, 8.5 Hz), 7.39 (s, 2H), 7.76 (s, 1H) ppm. MS: (MH)+558.

Workup

  1. washwashed twice with 2N NaOH
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered through a fritted funnel
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified on silica gel
  8. washeluted with a 1 to 5% linear gradient of (10% NH4OH-methanol)/DCM which

Sources & evidence

ORD record
ord-c00192254f0e447d81e43994f6dc4a18
Source dataset
uspto-grants-2010_01
Patent number
US07652058B2

Reaction notes

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