Hydrochloric Acid → [(1S)-5-({3-[4-(6,7-dihydro-5H-pyrano[2,3-d][1,3]thiazol-2-yl)-2-propylphenoxy]propyl}sulfanyl)-2,3-dihydro-1H-inden-1-yl]acetic acid

HRID 603516Notes

Reaction equation

HRID 603516 reaction equation
[S:1]1[C:5]2[CH2:6][CH2:7][CH2:8][O:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:35]=[CH:34][C:13]([O:14][CH2:15][CH2:16][CH2:17][S:18][C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][CH:27]=2)[C@H:24]([CH2:28][C:29]([O:31]CC)=[O:30])[CH2:23][CH2:22]3)=[C:12]([CH2:36][CH2:37][CH3:38])[CH:11]=1.C(O)C.[Li+].[OH-].Cl>C1COCC1.O>[S:1]1[C:5]2[CH2:6][CH2:7][CH2:8][O:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:35]=[CH:34][C:13]([O:14][CH2:15][CH2:16][CH2:17][S:18][C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][CH:27]=2)[C@H:24]([CH2:28][C:29]([OH:31])=[O:30])[CH2:23][CH2:22]3)=[C:12]([CH2:36][CH2:37][CH3:38])[CH:11]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 3939Lithium HydroxideHCID 86644243ethyl [(1S)-5-({3-[4-(6,7-dihydro-5H-pyrano[2,3-d][1,3]thiazol-2-yl)-2-propylphenoxy]propyl}thio)-2,3-dihydro-1H-inden-1-yl]acetate

Product 1

HCID 10481902[(1S)-5-({3-[4-(6,7-dihydro-5H-pyrano[2,3-d][1,3]thiazol-2-yl)-2-propylphenoxy]propyl}sulfanyl)-2,3-dihydro-1H-inden-1-yl]acetic acidYield 38.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl [(1S)-5-({3-[4-(6,7-dihydro-5H-pyrano[2,3-d][1,3]thiazol-2-yl)-2-propylphenoxy]propyl}sulfanyl)-2,3-dihydro-1H-inden-1-yl]acetate (50 mg, 0.09 mmol) (Example 509) in a mixture of THF (2 mL), ethanol (1 mL), and water (2 mL) was added LiOH (8.7 mg, 0.36 mmol). The reaction mixture was stirred vigorously at rt for 18 h, and then it was acidified to pH ˜2 using HCl (1M aqueous solution). The aqueous phase was extracted with CH2Cl2, and the combined organic phases were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (4:1 hexanes/EtOAc) to give the title compound (18 mg, 38%) as a white solid. 1H NMR (400 MHz, CDCl3) 7.64 (d, 1H), 7.62 (dd, 1H), 7.22 (s, 1H), 7.15 (d, 1H), 7.08 (d, 1H), 6.75 (d, 1H), 4.31 (t, 2H), 4.15-4.05 (m, 2H), 3.58-3.50 (m, 1H), 3.12 (t, 2H), 2.93-2.80 (m, 2H), 2.78 (t, 2H), 2.78-2.73 (m, 1H), 2.60 (t, 2H), 2.49 (dd, 1H), 2.45-2.36 (m, 1H), 2.17-2.06 (m, 4H), 1.81-1.73 (m, 1H), 1.68-1.58 (m, 2H), 0.95 (t, 3H); LC-MS: RT=4.54 min, (M+H)+ 524.2.

Workup

  1. extractionThe aqueous phase was extracted with CH2Cl2
  2. dry with materialthe combined organic phases were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel flash chromatography (4:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-5f0fa2ecfa924b52bcd9964aa7b0ae56
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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