Hydrochloric Acid → 3-Phenyl-3-{5-[2-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-ethoxy]-indol-1-yl}-propionic acid

HRID 24003Notes

Reaction equation

HRID 24003 reaction equation
C([O:3][C:4](=[O:35])[CH2:5][CH:6]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[N:7]1[C:15]2[C:10](=[CH:11][C:12]([O:16][CH2:17][CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[CH2:25][CH2:24][CH2:23][NH:22][C:21]=4[N:20]=3)=[CH:13][CH:14]=2)[CH:9]=[CH:8]1)C.C1COCC1.CO.O.O.[OH-].[Li+].Cl>C(OCC)(=O)C>[C:29]1([CH:6]([N:7]2[C:15]3[C:10](=[CH:11][C:12]([O:16][CH2:17][CH2:18][C:19]4[CH:28]=[CH:27][C:26]5[CH2:25][CH2:24][CH2:23][NH:22][C:21]=5[N:20]=4)=[CH:13][CH:14]=3)[CH:9]=[CH:8]2)[CH2:5][C:4]([OH:35])=[O:3])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 21892291Methanol tetrahydrofuran waterHCID 66821313HCID 66821313, compound

Product 1

HCID 101818153-Phenyl-3-{5-[2-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-ethoxy]-indol-1-yl}-propionic acidYield 66.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-phenyl-3-{5-[2-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-ethoxy]-indol-1-yl}-propionic acid ethyl ester (2.14 g, 4.49 mmol) in a 2:1:0.2 THF/MeOH/H2O (67 mL) was treated with lithium hydroxide monohydrate (0.38 g, 9.00 mmol) at room temperature. The reaction was stirred for 20 h. The mixture was diluted with ethyl acetate, acidified to pH 4 (0.5 N HCl), washed with water and brine, dried and concentrated to afford a crude mixture (2.02 g), which was purified by column chromatography with silica gel (39:1 to 29:1 dichloromethane/MeOH) to give the title compound (1.31 g, 66% yield). 1H NMR (CDCl3) δ 10.5 (s, 1H), 7.44 (d, 1H, J=3.1 Hz), 7.20-7.00 (m, 7H), 6.76 (m, 1H), 6.53 (dd, 1H, J=2.3, 6.6 Hz), 6.41 (s, 1H), 6.19 (d, 1H, J=7.3 Hz), 6.07 (dd, 1H, J=4.3, 7.1 Hz), 3.68 (m, 1H), 3.52 (m, 1H), 3.33 (m, 3H), 3.25-3.09 (m, 2H), 2.58 (m, 3H), 1.77 (m, 3H). Mass Spectrum (LCMS, ESI) calculated for C27H28N3O3 442.2 (M+H); found 442.3.

Workup

  1. washwashed with water and brine
  2. customdried
  3. concentrationconcentrated
  4. customto afford a crude mixture (2.02 g), which
  5. customwas purified by column chromatography with silica gel (39:1 to 29:1 dichloromethane/MeOH)

Sources & evidence

ORD record
ord-72e447f375d8481f8fe0997c4ef147dc
Source dataset
uspto-grants-2005_02
Patent number
US06855722B2

Reaction notes

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