Water → [(1S)-5-(3-{[6-(4-methoxyphenyl)-3-(trifluoromethyl)-2-pyridinyl]amino}propoxy)-2,3-dihydro-1H-inden-1-yl]acetic acid

HRID 603470Notes

Reaction equation

HRID 603470 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([NH:15][CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[C@H:25]([CH2:29][C:30]([O:32]CC)=[O:31])[CH2:24][CH2:23]4)[C:12]([C:35]([F:38])([F:37])[F:36])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.O.[Li+].[OH-]>C1COCC1.CO>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:14]=[C:13]([NH:15][CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[C@H:25]([CH2:29][C:30]([OH:32])=[O:31])[CH2:24][CH2:23]4)[C:12]([C:35]([F:37])([F:38])[F:36])=[CH:11][CH:10]=2)=[CH:7][CH:8]=1

Participants

6

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 59300468ethyl [(1S)-5-(3-{[6-(4-methoxyphenyl)-3-(trifluoromethyl)-2-pyridinyl]amino}propoxy)-2,3-dihydro-1H-inden-1-yl]acetate

Product 1

HCID 59300549[(1S)-5-(3-{[6-(4-methoxyphenyl)-3-(trifluoromethyl)-2-pyridinyl]amino}propoxy)-2,3-dihydro-1H-inden-1-yl]acetic acidYield 80%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl [(1S)-5-(3-{[6-(4-methoxyphenyl)-3-(trifluoromethyl)-2-pyridinyl]amino}propoxy)-2,3-dihydro-1H-inden-1-yl]acetate (Example 307) (0.05 g, 0.09 mmol) in THF (1 mL), methanol (1 mL), and water (0.5 mL) was added LiOH (0.02 g, 0.85 mmol). The mixture was stirred at rt for 18 h, and then concentrated under reduced pressure. The residue was taken up in water and acidified to pH ˜5 using H3PO4 (5% aqueous solution). The aqueous solution was then extracted with EtOAc. The combined organic phases were dried (Na2SO4), filtered, and then concentrated under reduced pressure to give the product (0.034 g, 80%). 1H NMR (400 MHz, CD2Cl2) δ 8.03 (d, 2H), 7.68 (d, 1H), 7.07 (dd, 2H), 6.97 (d, 2H), 6.80 (s, 1H), 6.72 (dd, 1H), 5.37 (b, 1H), 4.11 (t, 2H), 3.91-3.81 (m, 5H), 3.56-3.48 (m, 1H), 2.95-2.77 (m, 3H), 2.15-2.37 (m, 2H), 2.23-2.18 (m, 2H), 1.65-1.55 (m, 1H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. extractionThe aqueous solution was then extracted with EtOAc
  3. dry with materialThe combined organic phases were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-3205764ce9ce485ab7df1117930ce4aa
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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