Hydrochloric Acid → HCID 67118722, compound

HRID 1188991Notes

Reaction equation

HRID 1188991 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[CH:6]=[C:7]([O:25][C:26]2[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:28][CH:27]=2)[CH:8]=[C:9]2[C:13]=1[NH:12][C:11]([C:14]1[S:15][CH:16]([CH2:19]C(OCC)=O)[CH2:17][N:18]=1)=[CH:10]2)[CH3:3].[O:36]1[CH2:40][CH2:39]CC1.[CH3:41][Mg]Br.Cl>O1CCCC1>[CH3:41][C:40]([OH:36])([CH3:39])[CH2:19][CH:16]1[S:15][C:14]([C:11]2[NH:12][C:13]3[C:9]([CH:10]=2)=[CH:8][C:7]([O:25][C:26]2[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:33])=[O:34])=[CH:28][CH:27]=2)=[CH:6][C:5]=3[O:4][CH:2]([CH3:3])[CH3:1])=[N:18][CH2:17]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 68381853HCID 68381853, compoundHCID 178420675HCID 178420675, compound3×

Product 1

HCID 67118722HCID 67118722, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl (2-{7-(1-methylethoxy)-5-[4-(methylsulfonyl)phenoxy]-1H-indol-2-yl}-4,5-dihydro-1,3-thiazol-5-yl)acetate (490 mg) in tetrahydrofuran (10 mL) was added 1M methylmagnesium bromide tetrahydrofuran solution (7.6 mL) at 0° C. After the mixture was stirred at room temperature for 1.5 h, 1M methylmagnesium bromide tetrahydrofuran solution (3.4 mL) was added to the mixture again at room temperature. The mixture was stirred at room temperature for 2 h. Furthermore, 1M methylmagnesium bromide tetrahydrofuran solution (3.4 mL) was added to the mixture at room temperature and the mixture was stirred at room temperature for 30 min. The mixture was acidified with 1M hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=3/97 to 60/40, volume ratio) to give a yellow oil. The oil was crystallized from ethyl acetate-diethyl ether-hexane to give pale yellow crystals. The crystals were recrystallized from ethyl acetate-diisopropyl ether to give the title compound (50 mg, 10%) as pale yellow crystals. MS 503 (MH+).

Workup

  1. stirringThe mixture was stirred at room temperature for 2 h
  2. stirringthe mixture was stirred at room temperature for 30 min
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=3/97 to 60/40, volume ratio)
  9. customto give a yellow oil
  10. customThe oil was crystallized from ethyl acetate-diethyl ether-hexane
  11. customto give pale yellow crystals
  12. customThe crystals were recrystallized from ethyl acetate-diisopropyl ether

Sources & evidence

ORD record
ord-92d6f71f76c94fcaa3bfefe4a3b5188a
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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