p-Toluenesulfonic acid → HCID 24993956, compound

HRID 1393318Notes

Reaction equation

HRID 1393318 reaction equation
Cl.[F:2][C:3]([F:34])([F:33])[C:4]1[CH:5]=[C:6]([C@H:14]([O:16][C@H:17]2[CH2:25][CH2:24][C@@H:23]3[C@@H:19]([CH2:20][NH:21][CH2:22]3)[C@@H:18]2[C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[CH3:15])[CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1.[C:35]1(=O)[CH2:39][CH2:38][C:37](=[O:40])[CH2:36]1.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[F:34][C:3]([F:2])([F:33])[C:4]1[CH:5]=[C:6]([C@H:14]([O:16][C@H:17]2[CH2:25][CH2:24][C@@H:23]3[C@@H:19]([CH2:20][N:21]([C:35]4[CH2:39][CH2:38][C:37](=[O:40])[CH:36]=4)[CH2:22]3)[C@@H:18]2[C:26]2[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=2)[CH3:15])[CH:7]=[C:8]([C:10]([F:13])([F:11])[F:12])[CH:9]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 774661,3-CyclopentanedioneHCID 86613572HCID 86613572, compound

Product 1

HCID 24993956HCID 24993956, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 12.3 mg (0.26 mmol) of (3aR,4R,5S,7aR)-5-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}4-(4-fluorophenyl)octahydro-1H-isoindole (Example 2) in ˜2 mL dry toluene was added 2.7 mg (0.028 mmol) cyclopentane-1,3-dione and a catalytic amount (˜0.5 mg) of PTSA. The resulting mixture was heated at reflux for 16 hr. The solvent was removed vacuum and the residue was purified by prep TLC eluting with EtOAc/MeOH (95/5) to afford the title compound. 1H-NMR (CDCl3): δ: 7.73 (1 H, s), 7.20 (2 H, s), 7.03-6.90 (2 H, m), 4.98, 4.80 (1 H, s), 4.50 (1 H, m), 3.62-3.18 (2 H, m), 3.30-3.18 (3 H, m), 3.15, 2.97 (1 H, d, J=11.2 Hz), 2.68 (2 H, m), 2.55-2.40 (4 H, m), 2.17 (1 H, m), 2.20 (1 H, m), 2.00 (1 H, m), 1.85 (1 H, m), 1.62 (1 H, m), 1.33 (3 H, d, J=6.2 Hz). MS: (MH)+ 556.0.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 16 hr
  3. customThe solvent was removed vacuum
  4. customthe residue was purified by prep TLC
  5. washeluting with EtOAc/MeOH (95/5)

Sources & evidence

ORD record
ord-6e668fe5c85046e783c8c842915bddbc
Source dataset
uspto-grants-2008_03
Patent number
US07345083B2

Reaction notes

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