Hydrochloric Acid → (S)-2-(2-Oxo-4-p-tolyl-6-(4-(4,4,4-trifluorobutoxy)phenyl)-6-(trifluoromethyl)-1,2,5,6-tetrahydropyridin-3-yl)isoindoline-1,3-dione

HRID 1629795Notes

Reaction equation

[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][C:13]([NH:15][C@:16]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][CH2:40][C:41]([F:44])([F:43])[F:42])=[CH:33][CH:32]=1)([CH2:21][C:22](=O)[C:23]1[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=1)[C:17]([F:20])([F:19])[F:18])=[O:14].[OH-].[Na+].Cl>CO>[O:14]=[C:13]1[C:12]([N:3]2[C:4](=[O:11])[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[C:2]2=[O:1])=[C:22]([C:23]2[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=2)[CH2:21][C@:16]([C:31]2[CH:32]=[CH:33][C:34]([O:37][CH2:38][CH2:39][CH2:40][C:41]([F:43])([F:42])[F:44])=[CH:35][CH:36]=2)([C:17]([F:18])([F:19])[F:20])[NH:15]1

Participants

Conditions

Temperature: 69 °C

Procedure

Intermediate 104A (145 mg, 0.234 mmol) was dissolved in MeOH (2.2 mL) and then 1 N NaOH (0.2 mL) was added. The mixture was stirred at 69° C. for 45 min and added another 0.2 mL of 1 N NaOH. The reaction was heated at 130° C. under microwave conditions for 10 min. The mixture was neutralized with 1 N HCl and then concentrated. The residue was purified by silica gel chromatography (12 g silica gel, eluted with EtOAc in hexanes) to yield the desired product (80 mg, 57%). LCMS Anal. Calc'd for C31H24F6N2O4 602.16, found [M+H] 603.3.

Workup

temperatureThe reaction was heated at 130° C. under microwave conditions for 10 min
concentrationconcentrated
customThe residue was purified by silica gel chromatography (12 g silica gel, eluted with EtOAc in hexanes)

Sources & evidence

ORD record: ord-c003bfea3b5e449f80cb78be7be51962
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791091B2

Reaction notes

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