Morpholine → (4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[3-bromo-6-(morpholin-4-yl)pyridin-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

HRID 531240Notes

Reaction equation

HRID 531240 reaction equation
C(N(CC)CC)C.[NH:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.[F:14][C:15]([F:43])([F:42])[C:16]1[CH:17]=[C:18]([C@H:26]2[O:30][C:29](=[O:31])[N:28]([CH2:32][C:33]3[C:38]([Br:39])=[CH:37][CH:36]=[C:35](Cl)[N:34]=3)[C@H:27]2[CH3:41])[CH:19]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=1.O1CCOCC1>C(OCC)(=O)C>[F:25][C:22]([F:23])([F:24])[C:20]1[CH:19]=[C:18]([C@H:26]2[O:30][C:29](=[O:31])[N:28]([CH2:32][C:33]3[C:38]([Br:39])=[CH:37][CH:36]=[C:35]([N:8]4[CH2:13][CH2:12][O:11][CH2:10][CH2:9]4)[N:34]=3)[C@H:27]2[CH3:41])[CH:17]=[C:16]([C:15]([F:14])([F:42])[F:43])[CH:21]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 57576268(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one2×

Product 1

HCID 118021105(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[3-bromo-6-(morpholin-4-yl)pyridin-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-oneYield 82.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

Triethylamine (3.23 mL, 23.18 mmol), morpholine (1.683 mL, 19.32 mmol), (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 24, 2 g, 3.86 mmol) and 1,4-dioxane (10.0 mL) were mixed in a 20 mL microwave vial, capped and heated at 140° C. for 6 hours in microwave with monitoring by TLC and LCMS. Once the reaction was determined to be complete, the reaction mixture was diluted with ethyl acetate, washed with saturated aqueous NaHCO3, water and brine. The organic phase was dried with Na2SO4, filtered and the filtrate concentrated. The crude was purified by silica gel chromatography in 30% ethyl acetate/hexanes to give the titled compound (1.8 g, 3.17 mmol, 82% yield) as white solid. LCMS (M+H)+: 569.9. 1H NMR (CDCl3, 500 MHz): δ 7.93 (s, 1H), 7.80 (s, 2H), 7.63 (dd, 1H), 6.52 (d, 1H), 5.75 (d, 1H), 4.91 (d, 1H), 4.32 (d, 1H), 4.28 (t, 1H), 3.87-3.84 (t, 4H), 3.57-3.48 (m, 4H), 0.83 (d, 3H).

Workup

  1. customcapped
  2. washwashed with saturated aqueous NaHCO3, water and brine
  3. dry with materialThe organic phase was dried with Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated
  6. customThe crude was purified by silica gel chromatography in 30% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-e1e1320bff69448dadc996ae5f4e8bdc
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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