Phenol → Ethyl 5-(3-phenoxypropyl)-2-(1,2,3,4-tetrahydroquinolin-7-yl)thiazole-4-carboxylate

HRID 2178231Notes

Reaction equation

HRID 2178231 reaction equation
C([O-])([O-])=O.[K+].[K+].[C:7]1([OH:13])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C1OCCOCCOCCOCCOCCOC1.C(OC([N:39]1[C:48]2[C:43](=[CH:44][CH:45]=[C:46]([C:49]3[S:50][C:51]([CH2:59][CH2:60][CH2:61]I)=[C:52]([C:54]([O:56][CH2:57][CH3:58])=[O:55])[N:53]=3)[CH:47]=2)[CH2:42][CH2:41][CH2:40]1)=O)(C)(C)C.[H-].[Na+]>CN(C=O)C.CCOC(C)=O>[O:13]([CH2:61][CH2:60][CH2:59][C:51]1[S:50][C:49]([C:46]2[CH:47]=[C:48]3[C:43]([CH2:42][CH2:41][CH2:40][NH:39]3)=[CH:44][CH:45]=2)=[N:53][C:52]=1[C:54]([O:56][CH2:57][CH3:58])=[O:55])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

8

Reactant 5

HCID 996Phenol3×HCID 11430Potassium Carbonate2×HCID 24758Sodium hydrideHCID 2855718-Crown-6HCID 59418730Ethyl 2-(1-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroquinolin-7-yl)-5-(3-iodopropyl)thiazole-4-carboxylate

Product 1

HCID 59418748Ethyl 5-(3-phenoxypropyl)-2-(1,2,3,4-tetrahydroquinolin-7-yl)thiazole-4-carboxylateYield 22.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent2×

Procedure

To K2CO3 (32 mg, 0.23 mmol), phenol (28 mg, 0.30 mmol) and 18-crown-6 (180 mg, 0.70 mmol) was added DMF (1 mL). After 5 minutes ethyl 2-(1-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroquinolin-7-yl)-5-(3-iodopropyl)thiazole-4-carboxylate (23G) (129 mg, 0.23 mmol) in DMF (1 mL) was added to the reaction mixture and stirred at rt for 72 hours. The reaction was monitored by LCMS and starting material remained. To the reaction mixture was added K2CO3 (32 mg, 0.23 mmol) and phenol (28 mg, 0.30 mmol) and stirred at rt overnight. The reaction mixture was diluted with EtOAc, washed with saturated NaHCO3, water, brine, dried over MgSO4 and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel to provide 50 mg as a mixture of starting material and product. To DMF (1 mL) was added NaH (4 mg) and phenol (13 mg) and stirred for 10 minutes. To the reaction mixture was added the isolated material (50 mg) as a mixture of starting material and product and allowed to stir at rt overnight. The reaction mixture was diluted with EtOAc, washed with saturated NaHCO3, water, brine, dried with MgSO4 and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel to provide 22 mg of the desired product.

Workup

  1. stirringstirred at rt overnight
  2. washwashed with saturated NaHCO3, water, brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude material was purified by column chromatography on silica gel
  6. customto provide 50 mg
  7. additionas a mixture of starting material and product
  8. stirringstirred for 10 minutes
  9. additionas a mixture of starting material and product
  10. stirringto stir at rt overnight
  11. washwashed with saturated NaHCO3, water, brine
  12. dry with materialdried with MgSO4
  13. concentrationconcentrated under reduced pressure
  14. customThe crude material was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-319cf6cb99ea45618e6b8e58b2479bb8
Source dataset
uspto-grants-2015_06
Patent number
US09067928B2

Reaction notes

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