Acetic Acid → (+/-)-[10-(4-Chlorophenyl)-1-(methylsulfinyl)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl]acetic acid
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[S:17]([CH3:19])=[O:18])[N:10]3[CH2:20][CH2:21][CH2:22][CH:23]([CH2:24][C:25]([O:27]CC)=[O:26])[C:9]=23)=[CH:4][CH:3]=1.C1COCC1.CO.[Li+].[OH-].CC(O)=O>[Cl-].[Na+].O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[S:17]([CH3:19])=[O:18])[N:10]3[CH2:20][CH2:21][CH2:22][CH:23]([CH2:24][C:25]([OH:27])=[O:26])[C:9]=23)=[CH:4][CH:3]=1Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of the ester of Step 13 in a THF/MeOH (3:1) mixture at r.t. was added 1N LiOH (aqueous solution). The reaction mixture was stirred at r.t. for 2 hours and AcOH (0.5 mL) and brine (5 mL) were added. The aqueous layer was extracted with EtOAc and the combined organic layers were dried over Na2SO4 and concentrated. The residue was swished in EtOAc/hexanes to give the desired acid as a white solid. Each isomer from Step 13 was hydrolyzed under these conditions. From the less polar diastereomer of Step 13: 1H NMR (methanol-d4) δ 7.65 (1H, d), 7.61 (1H, d), 7.51–7.35 (5H, m), 4.37–4.29 (1H, m), 4.09–4.02 (1H, m), 3.79–3.71 (1H, m), 2.40 (1H, dd), 2.24 (3H, s), 2.23–1.91 (5H, m). MS (−APCI) m/z 400.2 M-H)+.
Workup
- extractionThe aqueous layer was extracted with EtOAc
- dry with materialthe combined organic layers were dried over Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-3dc39eb59842496ead6dfa0603a4fc29
- Source dataset
- uspto-grants-2006_12
- Patent number
- US07144913B2
Reaction notes
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