Sodium Bicarbonate → E-(6-{2-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]vinyl}-[(4R,6S)-2,2-dimethyl-[1,3]dioxan-4-yl])-N-methoxy-N-methyl-acetamide

HRID 445946Notes

Reaction equation

HRID 445946 reaction equation
[CH3:1][C:2]1([CH3:30])[O:7][C@@H:6]([CH2:8][C:9]([N:11]([O:13][CH3:14])[CH3:12])=[O:10])[CH2:5][C@@H:4]([CH2:15]S(C2N(C3C=CC=CC=3)N=NN=2)(=O)=O)[O:3]1.[CH:31]1([C:34]2[C:43]([CH:44]=O)=[C:42]([C:46]3[CH:51]=[CH:50][C:49]([F:52])=[CH:48][CH:47]=3)[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[N:35]=2)[CH2:33][CH2:32]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C(=O)(O)[O-].[Na+]>O1CCCC1>[CH:31]1([C:34]2[C:43](/[CH:44]=[CH:15]/[C@H:4]3[O:3][C:2]([CH3:1])([CH3:30])[O:7][C@@H:6]([CH2:8][C:9]([N:11]([O:13][CH3:14])[CH3:12])=[O:10])[CH2:5]3)=[C:42]([C:46]3[CH:51]=[CH:50][C:49]([F:52])=[CH:48][CH:47]=3)[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[N:35]=2)[CH2:32][CH2:33]1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 2733832Lithium HexamethyldisilazideHCID 99479742-Cyclopropyl-4-(4-fluorophenyl)-3-quinolinecarboxaldehydeHCID 566023362-((4R,6S)-2,2-dimethyl-6-(((1-phenyl-1H-tetrazol-5-yl)sulfonyl)methyl)-1,3-dioxan-4-yl)-N-methoxy-N-methylacetamide

Product 1

HCID 86761897E-(6-{2-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]vinyl}-[(4R,6S)-2,2-dimethyl-[1,3]dioxan-4-yl])-N-methoxy-N-methyl-acetamideYield 90.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

2-[(4R,6S)-2,2-dimethyl-6-(1-phenyl-1H-tetrazole-5-sulfonylmethyl)-[1,3]dioxan-4-yl]-N-methoxy-N-methyl-acetamide (16.6 g), 2-cyclopropyl-3-formyl-4-(4-fluorophenyl)quinoline (10.0 g), and tetrahydrofuran (400.0 mL) were added to a reactor and then the reaction mixture was cooled to −70° C. A solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (1M, 36.0 mL) was slowly added to the reaction mixture, the temperature of which was adjusted to −20˜−10° C. The reaction mixture was stirred at the same temperature for 1 hour and then 8% sodium bicarbonate solution (80.0 mL) was added thereto under stirring. The separated organic layer was washed with water (60.0 mL) and then concentrated under reduced pressure to obtain E-(6-{2-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]vinyl}-[(4R,6S)-2,2-dimethyl-[1,3]dioxan-4-yl])-N-methoxy-N-methyl-acetamide as a solid (15.6 g, yield 90%).

Workup

  1. customwas adjusted to −20˜−10° C
  2. stirringunder stirring
  3. washThe separated organic layer was washed with water (60.0 mL)
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-46459cccef074c5895349565a7137906
Source dataset
uspto-grants-2013_07
Patent number
US08476432B2

Reaction notes

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