Ethyl Acetate → HCID 68001476, compound

HRID 534250Notes

Reaction equation

HRID 534250 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([C:20]3[CH:35]=[CH:34][C:23]([O:24][CH2:25][C@@H:26]([N:28]4[CH2:32][CH2:31][C@@H:30]([CH3:33])[CH2:29]4)[CH3:27])=[CH:22][CH:21]=3)=[C:8]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[CH2:9]2)=[CH:5][CH:4]=1.C(OCC)(=O)C>[Pd].C(O)C>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6](=[CH:5][CH:4]=1)[CH:7]([C:20]1[CH:21]=[CH:22][C:23]([O:24][CH2:25][C@@H:26]([N:28]3[CH2:32][CH2:31][C@@H:30]([CH3:33])[CH2:29]3)[CH3:27])=[CH:34][CH:35]=1)[CH:8]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)[CH2:9]2

Participants

5

Reactant 2

HCID 8857Ethyl AcetateHCID 68000125HCID 68000125, compound

Product 1

HCID 68001476HCID 68001476, compoundYield 85.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A mixture of (R)-1-((S)-1-(4-(6-methoxy-2-(4-methoxyphenyl)-1H-inden-3-yl)phenoxy)propan-2-yl)-3-methylpyrrolidine (400 mg, 0.85 mmol), 10% Pd/C (350 mg, 0.33 mmol), ethyl acetate (8 mL), and ethanol (8 mL) was shaken at 65 psi of H2 for 25 h. The sides of the reaction vessel were rinsed (4 mL, 1:1 EtOAc/EtOH), and the mixture was shaken at 65 psi of H2 for an additional 22.5 h. The reaction was filtered through Celite. The Celite was washed (200 mL, 1:1 EtOAc/EtOH), and the filtrate was concentrated and purified by silica gel chromatography (1:0→17:3; dichloromethane:methanol) to give 343 mg of (3R)-1-((2S)-1-(4-(5-methoxy-2-(4-methoxyphenyl)-2,3-dihydro-1H-inden-1-yl)phenoxy)propan-2-yl)-3-methylpyrrolidine: 1H NMR (400 MHz, DMSO-d6): δ 6.99 (d, 1H), 6.92 (d, 1H), 6.80 (d, 2H), 6.74 (dd, 1H), 6.66-6.57 (m, 4H), 6.50 (d, 2H), 4.51 (d, 1H), 3.96-3.87 (m, 2H), 3.77 (s, 3H), 3.63 (s, 3H), 3.70-3.60 (br, 1H), 3.26 (dd, 1H), 3.12 (dd, 1H), 2.81 (br, 1H), 2.70-2.50 (br, 3H), 2.07 (br, 2H), 1.88 (br, 1H), 1.24 (br, 1H), 1.07 (br d, 3H), 0.96 (d, 3H); LCMS: 472.8 (M+H)+.

Workup

  1. washThe sides of the reaction vessel were rinsed (4 mL, 1:1 EtOAc/EtOH)
  2. stirringthe mixture was shaken at 65 psi of H2 for an additional 22.5 h
  3. filtrationThe reaction was filtered through Celite
  4. washThe Celite was washed (200 mL, 1:1 EtOAc/EtOH)
  5. concentrationthe filtrate was concentrated
  6. custompurified by silica gel chromatography (1:0→17:3; dichloromethane:methanol)

Sources & evidence

ORD record
ord-bc73c8caa15a4ee3955bce777e3bf3c8
Source dataset
uspto-grants-2014_10
Patent number
US08853423B2

Reaction notes

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