Iodine → diethyl[(4R,9aS)-6-oxo-4-(3,4,5-trifluorophenyl)octahydropyrido[2,1-c][1,4]oxazin-7-yl]phosphonate

HRID 16351

Reaction equation

HRID 16351 reaction equation
[I-].[F:2][C:3]1[CH:4]=[C:5]([C@@H:11]2[CH2:16][O:15][CH2:14][C@@H:13]3[CH2:17][CH2:18][CH2:19][C:20](=[O:21])[N:12]23)[CH:6]=[C:7]([F:10])[C:8]=1[F:9].CN(C)CCN(C)C.II.S([O-])([O-])(=O)=S.[Na+].[Na+].[P:39]([O:46]CC)([O:43][CH2:44][CH3:45])[O:40][CH2:41][CH3:42]>C(OCC)(=O)C.C(Cl)Cl>[CH2:41]([O:40][P:39]([CH:19]1[C:20](=[O:21])[N:12]2[C@H:13]([CH2:14][O:15][CH2:16][C@H:11]2[C:5]2[CH:6]=[C:7]([F:10])[C:8]([F:9])=[C:3]([F:2])[CH:4]=2)[CH2:17][CH2:18]1)(=[O:46])[O:43][CH2:44][CH3:45])[CH3:42]

Participants

9

Reactant 6

HCID 807IodineHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 24477Sodium ThiosulfateHCID 30165Iodide IonHCID 31215Triethyl phosphiteHCID 44124045(4R,9aS)-4-(3,4,5-Trifluorophenyl)hexahydropyrido[2,1-c][1,4]oxazin-6(1H)-one

Product 1

HCID 86612713diethyl[(4R,9aS)-6-oxo-4-(3,4,5-trifluorophenyl)octahydropyrido[2,1-c][1,4]oxazin-7-yl]phosphonate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

In nitrogen atmosphere, trimethylsilyle iodide (0.188 mL) was added to a methylene chloride solution (6 mL) of (4R,9aS)-4-(3,4,5-trifluorophenyl)hexahydropyrido[2,1-c][1,4]oxazin-6-one (252 mg) and N,N,N′,N′-tetramethylethylenediamine (0.466 mL) at 0° C. The resulting reaction solution was stirred under ice-cooling for 30 min, and iodine (336 mg) was added thereto under ice-cooling. The resulting reaction solution was stirred under ice-cooling for 1 hr, and ethyl acetate and a saturated sodium thiosulfate aqueous solution were added thereto. The organic layer was separated, washed with saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure to give a crude iodinated substance. To the given crude iodinated substance, triethyl phosphite (3 mL) was added. The resulting mixture was stirred at 120° C. for 2 hr, allowed to cool to room temperature, and then concentrated under reduced pressure to give 372 mg of the title compound. The physical property values of this compound were as follows:

Workup

  1. customThe resulting reaction solution
  2. temperaturecooling for 30 min
  3. temperatureunder ice-cooling
  4. customThe resulting reaction solution
  5. stirringwas stirred under ice-
  6. temperaturecooling for 1 hr
  7. customThe organic layer was separated
  8. washwashed with saturated saline
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customto give a crude
  12. additionwas added
  13. stirringThe resulting mixture was stirred at 120° C. for 2 hr
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b821cd62ac954a23a425bea5b716d3b4
Source dataset
uspto-grants-2010_06
Patent number
US07737141B2

Linked notes

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