(Diethylamino)sulfur trifluoride → (S)-methyl 6-(2-(1-(tert-butoxycarbonyl)-3-fluoro azetidin-3-yl)thiazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

HRID 1051725Notes

Reaction equation

HRID 1051725 reaction equation
C(N(S(F)(F)[F:7])CC)C.[C:10]([O:14][C:15]([N:17]1[CH2:20][C:19]([C:22]2[S:23][CH:24]=[C:25]([C:27]3[C:28]([O:42][CH:43]4[CH2:46][CH2:45][CH2:44]4)=[C:29]4[C:34](=[CH:35][CH:36]=3)[N:33]([C:37]([O:39][CH3:40])=[O:38])[C@@H:32]([CH3:41])[CH2:31][CH2:30]4)[N:26]=2)(O)[CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].C(=O)(O)[O-].[Na+]>ClCCl>[C:10]([O:14][C:15]([N:17]1[CH2:20][C:19]([C:22]2[S:23][CH:24]=[C:25]([C:27]3[C:28]([O:42][CH:43]4[CH2:46][CH2:45][CH2:44]4)=[C:29]4[C:34](=[CH:35][CH:36]=3)[N:33]([C:37]([O:39][CH3:40])=[O:38])[C@@H:32]([CH3:41])[CH2:31][CH2:30]4)[N:26]=2)([F:7])[CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]

Participants

5

Reactant 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 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 118075426(S)-methyl 6-(2-(1-(tert-butoxycarbonyl)-3-fluoro azetidin-3-yl)thiazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylateYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

(Diethylamino)sulfur trifluoride (DAST) (0.152 g, 0.94 mmol) was added to a −78° C. 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 dichloromethane (4 mL), and the resulting solution stirred for 2 h at −78° C. The reaction mixture was poured into saturated aqueous sodium bicarbonate solution (20 mL) and extracted with dichloromethane (3×20 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via preparative thin layer chromatography (eluting with 30% ethyl acetate/petroleum ether) to afford (S)-methyl 6-(2-(1-(tert-butoxycarbonyl)-3-fluoro azetidin-3-yl)thiazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (0.059 g, 59%) as a yellow solid. MS (ESI, pos. ion) m/z 532 [M+H]+.

Workup

  1. extractionextracted with dichloromethane (3×20 mL)
  2. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified via preparative thin layer chromatography (eluting with 30% ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-8a94e2ec00bf472eb695fc4f75843269
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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