Hydrochloric Acid → ethyl [(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

HRID 603515Notes

Reaction equation

HRID 603515 reaction equation
CN(C)[C:3]([S:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[C@H:11]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:10][CH2:9]2)=O.[O-:22][CH2:23][CH3:24].[Na+].BrCCC[C:30]1[CH:35]=[CH:34][C:33]([C:36]2[S:37][C:38]3[CH2:44][CH2:43][CH2:42][O:41][C:39]=3[N:40]=2)=[CH:32][C:31]=1[CH2:45][CH2:46][CH3:47].Cl>CN(C=O)C.[Cl-].[Na+].O>[S:37]1[C:38]2[CH2:44][CH2:43][CH2:42][O:41][C:39]=2[N:40]=[C:36]1[C:33]1[CH:34]=[CH:35][C:30]([O:22][CH2:23][CH2:24][CH2:3][S:5][C:6]2[CH:7]=[C:8]3[C:12](=[CH:13][CH:14]=2)[C@H:11]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:10][CH2:9]3)=[C:31]([CH2:45][CH2:46][CH3:47])[CH:32]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 2723922Sodium ethoxideHCID 59300457ethyl ((1S)-5-{[(dimethylamino)carbonyl]sulfanyl}-2,3-dihydro-1H-inden-1-yl)acetateHCID 670189722[4-(3-bromopropyl)-3-propylphenyl]-6,7-dihydro-5H-pyrano(2,3-d]thiazole

Product 1

HCID 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]acetateYield 33.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of ethyl ((1S)-5-{[(dimethylamino)carbonyl]sulfanyl}-2,3-dihydro-1H-inden-1-yl)acetate (130 mg, 0.42 mmol) (Example 508) in DMF (5 mL) was added sodium ethoxide (0.63 mL, 1.69 mmol, 21% solution in EtOH), and the reaction mixture was stirred at rt. The solution turned purple, and after 2 h, the starting material had been consumed. A solution preparation of 2[4-(3-bromopropyl)-3-propylphenyl]-6,7-dihydro-5H-pyrano{2,3-d]thiazole (119 mg, 0.30 mmol) (Example 506) in DMF (1.5 mL) was added. After an additional 2 h of stirring at rt, HCl (4 mL, 1N aqueous solution) was added, followed by brine. The aqueous phase was extracted with ether, and the combined organic phases were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (8:1 hexanes/EtOAc) to give the title compound (55 mg, 33%). 1H NMR (400 MHz, CDCl3) 7.67 (d, 1H), 7.62 (dd, 1H), 7.21 (s, 1H), 7.15 (d, 1H), 7.07 (d, 1H), 6.77 (d, 1H), 4.30 (t, 2H), 4.17 (q, 2H), 4.08 (t, 2H), 3.58-3.48 (m, 1H), 3.11 (t, 2H), 2.92-2.73 (m, 2H), 2.77 (t, 2H), 2.72 (dd, 1H), 2.60 (t, 2H), 2.44-2.32 (m, 2H), 2.16-2.03 (m, 4H), 1.79-1.68 (m, 1H), 1.67-1.57 (m, 2H), 1.28 (t, 3H), 0.94 (t, 3H); LC-MS: RT=4.85 min, (M+H)+ 552.2.

Workup

  1. customthe starting material had been consumed
  2. additionwas added
  3. stirringAfter an additional 2 h of stirring at rt
  4. extractionThe aqueous phase was extracted with ether
  5. dry with materialthe combined organic phases were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel flash chromatography (8:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-020efdb3527d4cecbff0bbb0c915a7f5
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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