Water → (S)-methyl 6-(2-(1-(tert-butoxycarbonyl)-3-methoxyazetidin-3-yl)thiazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

HRID 1051727Notes

Reaction equation

HRID 1051727 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:13][C:12]([C:15]2[S:16][CH:17]=[C:18]([C:20]3[C:21]([O:35][CH:36]4[CH2:39][CH2:38][CH2:37]4)=[C:22]4[C:27](=[CH:28][CH:29]=3)[N:26]([C:30]([O:32][CH3:33])=[O:31])[C@@H:25]([CH3:34])[CH2:24][CH2:23]4)[N:19]=2)([OH:14])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:40]I.O>CN(C)C=O>[C:3]([O:7][C:8]([N:10]1[CH2:13][C:12]([C:15]2[S:16][CH:17]=[C:18]([C:20]3[C:21]([O:35][CH:36]4[CH2:37][CH2:38][CH2:39]4)=[C:22]4[C:27](=[CH:28][CH:29]=3)[N:26]([C:30]([O:32][CH3:33])=[O:31])[C@@H:25]([CH3:34])[CH2:24][CH2:23]4)[N:19]=2)([O:14][CH3:40])[CH2:11]1)=[O:9])([CH3:4])([CH3:5])[CH3:6]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 118076304(S)-methyl 6-(2-(1-(tert-butoxycarbonyl)-3-hydroxyazetidin-3-yl)thiazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Product 1

HCID 118076519(S)-methyl 6-(2-(1-(tert-butoxycarbonyl)-3-methoxyazetidin-3-yl)thiazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil, 0.012 g, 0.30 mmol) was added to a solution of (S)-methyl 6-(2-(1-(tert-butoxycarbonyl)-3-hydroxyazetidin-3-yl)thiazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (0.100 g, 0.19 mmol) in N,N-dimethylformamide (2 mL), and the resulting mixture was stirred for 30 min at room temperature. Methyl iodide (0.014 mL, 0.23 mmol) was added, and the resulting mixture s stirred overnight at room temperature. The reaction mixture was poured into 10 mL of water, extracted with 3×10 mL of ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by Prep-TLC with ethyl acetate/petroleum ether (13). This resulted in 70 mg (68%) of (S)-methyl 6-(2-(1-(tert-butoxycarbonyl)-3-methoxyazetidin-3-yl)thiazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate as colorless oil. MS (ESI, pos. ion) m/z 544 [M+H]+.

Workup

  1. stirringthe resulting mixture s stirred overnight at room temperature
  2. extractionextracted with 3×10 mL of ethyl acetate
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by Prep-TLC with ethyl acetate/petroleum ether (13)
  6. customThis resulted in 70 mg (68%) of (S)-methyl 6-(2-(1-(tert-butoxycarbonyl)-3-methoxyazetidin-3-yl)thiazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate as colorless oil

Sources & evidence

ORD record
ord-0763ea88cd5c4e7886ef438e705b4ba5
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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