Hydrochloric Acid → methyl (Z)-3-[(3S,5R)-4-(3-butenoyl)-5-(3,4,5-trifluorophenyl)morpholin-3-yl]acrylate

HRID 553963Notes

Reaction equation

HRID 553963 reaction equation
[CH:1]([CH2:3][C:4](O)=[O:5])=[CH2:2].C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.[F:22][C:23]1[CH:24]=[C:25]([C@H:31]2[NH:36][C@@H:35]([CH:37]=[CH:38][C:39]([O:41][CH3:42])=[O:40])[CH2:34][O:33][CH2:32]2)[CH:26]=[C:27]([F:30])[C:28]=1[F:29].Cl>C1COCC1.C(OCC)(=O)C.C(N(CC)CC)C>[C:4]([N:36]1[C@H:31]([C:25]2[CH:26]=[C:27]([F:30])[C:28]([F:29])=[C:23]([F:22])[CH:24]=2)[CH2:32][O:33][CH2:34][C@@H:35]1/[CH:37]=[CH:38]/[C:39]([O:41][CH3:42])=[O:40])(=[O:5])[CH2:3][CH:1]=[CH2:2].[C:4]([N:36]1[C@H:31]([C:25]2[CH:26]=[C:27]([F:30])[C:28]([F:29])=[C:23]([F:22])[CH:24]=2)[CH2:32][O:33][CH2:34][C@@H:35]1/[CH:37]=[CH:38]\[C:39]([O:41][CH3:42])=[O:40])(=[O:5])[CH2:3][CH:1]=[CH2:2]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 327433-Butenoic acidHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 67461465methyl 3-[(3S,5R)-5-(3,4,5-trifluorophenyl)morpholin-3-yl]acrylate

Product 2

HCID 67461698methyl (Z)-3-[(3S,5R)-4-(3-butenoyl)-5-(3,4,5-trifluorophenyl)morpholin-3-yl]acrylateHCID 67463888methyl (E)-3-[(3S,5R)-4-(3-butenoyl)-5-(3,4,5-trifluorophenyl)morpholin-3-yl]acrylate

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

Triethylamine (0.2 mL), vinylacetic acid (0.09 mL), and BOPCl (275 mg) were sequentially added to a solution of methyl 3-[(3S,5R)-5-(3,4,5-trifluorophenyl)morpholin-3-yl]acrylate (217 mg) in THF (5 mL) at 0° C., and the reaction solution was stirred at room temperature for two hours. Ethyl acetate and 0.5 N hydrochloric acid were added to the reaction solution, and the organic layer was separated. The resulting organic layer was sequentially washed with a 0.5 N sodium hydroxide solution and brine, dried over magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel chromatography (elution solvent: heptane->heptane:ethyl acetate=1:1) to obtain 110 mg of methyl (E)-3-[(3S,5R)-4-(3-butenoyl)-5-(3,4,5-trifluorophenyl)morpholin-3-yl]acrylate and 132 mg of methyl (Z)-3-[(3S,5R)-4-(3-butenoyl)-5-(3,4,5-trifluorophenyl)morpholin-3-yl]acrylate. The property values of the isomers are as follows.

Workup

  1. customthe organic layer was separated
  2. washThe resulting organic layer was sequentially washed with a 0.5 N sodium hydroxide solution and brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography (elution solvent: heptane->heptane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-8cb8922baf654b1ab9c0ea1b26d122a2
Source dataset
uspto-grants-2011_11
Patent number
US08048878B2

Reaction notes

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