1,1'-Carbonyldiimidazole → Methyl3,3-dimethyl-2-(3-(methylsulfonylcarbamoyl)phenyl)-1,2,3,4-tetrahydroquinoline-6-carboxylate

HRID 2045558Notes

Reaction equation

HRID 2045558 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]([C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=1)[C:18]([OH:20])=O)[C:9]([CH3:25])([CH3:24])[CH2:8]2)=[O:4].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:38][S:39]([NH2:42])(=[O:41])=[O:40].N12CCCN=C1CCCCC2>O1CCCC1.C(OCC)(=O)C>[CH3:24][C:9]1([CH3:25])[CH2:8][C:7]2[C:12](=[CH:13][CH:14]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:6]=2)[NH:11][CH:10]1[C:15]1[CH:23]=[CH:22][CH:21]=[C:17]([C:18](=[O:20])[NH:42][S:39]([CH3:38])(=[O:41])=[O:40])[CH:16]=1

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 674419763-(6-(Methoxycarbonyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinolin-2-yl)benzoic acid

Product 1

HCID 67441518Methyl3,3-dimethyl-2-(3-(methylsulfonylcarbamoyl)phenyl)-1,2,3,4-tetrahydroquinoline-6-carboxylateYield 111.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-(6-(methoxycarbonyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinolin-2-yl)benzoic acid (150 mg, 0.44 mmol) and 1,1′-carbonyldiimidazole (214 mg, 1.32 mmol) in tetrahydrofuran (3 mL) was heated to 60° C. for 2 h, then was cooled to room temperature and treated with methanesulfonamide (54.2 mg, 0.57 mmol, 1.3 eq.). After stirring for 10 min, the reaction mixture was treated with dropwise addition of a solution of 1,8-diazabicyclo[5.4.0]undec-7-ene (221 mg, 1.45 mmol) in tetrahydrofuran (1 mL). Upon completion of addition, the resultant mixture was stirred overnight. Thin layer chromatography (petroleum ether:ethyl acetate=1:1) showed the reaction was complete. The reaction mixture was quenched with brine and acidified with 1N hydrochloric acid solution to pH=5, extracted with ethyl acetate (twice). The combined organic layers were washed with brine for 3 times, dried over anhydrous sodium sulfate. Removal of the solvent in vacuo gave 205 mg of methyl 3,3-dimethyl-2-(3-(methylsulfonylcarbamoyl)phenyl)-1,2,3,4-tetrahydroquinoline-6-carboxylate as a white solid, which was purified by column chromatography (petroleum ether: ethyl acetate=2:1 to 1:1) to afford 58 mg of white solid, which was used in next step.

Workup

  1. additionUpon completion of addition
  2. customThe reaction mixture was quenched with brine
  3. extractionextracted with ethyl acetate (twice)
  4. washThe combined organic layers were washed with brine for 3 times
  5. dry with materialdried over anhydrous sodium sulfate
  6. customRemoval of the solvent in vacuo

Sources & evidence

ORD record
ord-5368cc05814b4a72af6b5839ed6e62a4
Source dataset
uspto-grants-2013_11
Patent number
US08586747B2

Reaction notes

Loading…