Hydrochloric Acid → methyl (S)-5-cyclobutoxy-6-(2-(4-hydroxypiperidin-4-yl)thiazol-4-yl)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

HRID 1051648Notes

Reaction equation

HRID 1051648 reaction equation
Cl.C(OC([N:9]1[CH2:14][CH2:13][C:12]([C:16]2[S:17][CH:18]=[C:19]([C:21]3[C:22]([O:36][CH:37]4[CH2:40][CH2:39][CH2:38]4)=[C:23]4[C:28](=[CH:29][CH:30]=3)[N:27]([C:31]([O:33][CH3:34])=[O:32])[C@@H:26]([CH3:35])[CH2:25][CH2:24]4)[N:20]=2)([OH:15])[CH2:11][CH2:10]1)=O)(C)(C)C>O1CCOCC1>[CH:37]1([O:36][C:22]2[C:21]([C:19]3[N:20]=[C:16]([C:12]4([OH:15])[CH2:11][CH2:10][NH:9][CH2:14][CH2:13]4)[S:17][CH:18]=3)=[CH:30][CH:29]=[C:28]3[C:23]=2[CH2:24][CH2:25][C@H:26]([CH3:35])[N:27]3[C:31]([O:33][CH3:34])=[O:32])[CH2:38][CH2:39][CH2:40]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 118075548(S)-methyl 6-(2-(1-(tert-butoxycarbonyl)-4-hydroxypiperidin-4-yl)thiazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Product 1

HCID 131736100methyl (S)-5-cyclobutoxy-6-(2-(4-hydroxypiperidin-4-yl)thiazol-4-yl)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylateYield 59%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

HCl (4 M in 1,4-dioxane, 0.58 mL, 2.30 mmol) was added to a solution of (S)-methyl 6-(2-(1-(tert-butoxycarbonyl)-4-hydroxypiperidin-4-yl)thiazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (0.128 g, 0.230 mmol) in 1,4-dioxane (1.0 mL), and the reaction mixture stirred at rt for 1 h. The reaction mixture was concentrated and the residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The aqueous phase was separated and extracted with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was dissolved in dichloromethane and then filtered through a plug of silica gel (eluting with 10% ethanol-ethyl acetate). The filtrate was concentrated to afford methyl (S)-5-cyclobutoxy-6-(2-(4-hydroxypiperidin-4-yl)thiazol-4-yl)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (62 mg, 59%). 1H NMR (300 MHz, DMSO-d6) 6 ppm 1.11 (d, J=6.45 Hz, 3H), 1.22-1.72 (m, 6H), 1.93-2.24 (m, 7H), 2.39-2.49 (m, 2H), 2.71-2.96 (m, 4H), 3.69 (s, 3H), 4.05-4.20 (m, 1H), 4.47 (dq, J=13.05, 6.50 Hz, 1H), 5.88 (s, 1H), 7.33 (d, J=8.79 Hz, 1H), 7.69 (d, J=8.50 Hz, 1H), 7.77 (s, 1H). MS (ESI, pos. ion) m/z 458 [M+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
  3. customThe aqueous phase was separated
  4. extractionextracted with ethyl acetate
  5. dry with materialThe combined organic phases were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in dichloromethane
  9. filtrationfiltered through a plug of silica gel (eluting with 10% ethanol-ethyl acetate)
  10. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-7f2f746993df40118f03c5bc03e7c85f
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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