Lithium Hydroxide → ((1S)-6-(((2-(butyloxy)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetic acid

HRID 2098967Notes

Reaction equation

HRID 2098967 reaction equation
[CH2:1]([O:5][C:6]1[CH:11]=[C:10]([CH2:12][O:13][C:14]2[CH:22]=[C:21]3[C:17]([CH2:18][CH2:19][C@H:20]3[CH2:23][C:24]([O:26]C)=[O:25])=[CH:16][CH:15]=2)[CH:9]=[CH:8][C:7]=1[C:28]1[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[CH:30][C:29]=1[F:36])[CH2:2][CH2:3][CH3:4].[OH-].[Li+]>C1COCC1.CO>[CH2:1]([O:5][C:6]1[CH:11]=[C:10]([CH2:12][O:13][C:14]2[CH:22]=[C:21]3[C:17]([CH2:18][CH2:19][C@@H:20]3[CH2:23][C:24]([OH:26])=[O:25])=[CH:16][CH:15]=2)[CH:9]=[CH:8][C:7]=1[C:28]1[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[CH:30][C:29]=1[F:36])[CH2:2][CH2:3][CH3:4].[CH2:1]([O:5][C:6]1[CH:11]=[C:10]([CH2:12][O:13][C:14]2[CH:22]=[C:21]3[C:17]([CH2:18][CH2:19][C@H:20]3[CH2:23][C:24]([OH:26])=[O:25])=[CH:16][CH:15]=2)[CH:9]=[CH:8][C:7]=1[C:28]1[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[CH:30][C:29]=1[F:36])[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 59590932methyl ((1S)-6-(((2-(butyloxy)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetate

Product 2

HCID 44223268((1R)-6-(((2-(butyloxy)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetic acidHCID 44223269((1S)-6-(((2-(butyloxy)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetic acidYield 84.4%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of 17.1 (0.024 g, 0.0485 mmol) in THF/MeOH (2/1) (1.5 mL) was added lithium hydroxide (0.50 mL, 0.50 mmol). The resulting mixture was stirred overnight at 23° C., quenched with excess 1N HCl, and extracted with EtOAc. The combined organic layers were dried over anhydrous Na2SO4 and concentrated. The residue was purified by silica gel chromatography (0 to 40% EtOAc/hexanes) to afford ((1R)-6-(((2-(butyloxy)-2′-fluoro-5′-(methyloxy)-1,1′-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetic acid or ((1S)-6-(((2-(butyloxy)-2′-fluoro-5′-(methyloxy)-1,1′-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetic acid 17 (0.0098 g, 42% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.26-7.31 (1H, m), 7.15 (1H, d, J=7.8 Hz), 7.00-7.09 (3H, m), 6.81-6.90 (4H, m), 5.07 (2H, s), 4.00 (2H, t, J=6.5 Hz), 3.80 (3H, s), 3.59 (1H, m), 2.78-2.94 (3H, m), 2.55-2.40 (2H, m), 1.86-1.76 (1H, m), 1.64-1.71 (2H, m), 1.33-1.43 (2H, m), 0.89 (3H, t, J=7.4 Hz).

Workup

  1. customquenched with excess 1N HCl
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography (0 to 40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-62b6f9598fb746cea25a7429c1daa031
Source dataset
uspto-grants-2013_05
Patent number
US08450522B2

Reaction notes

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