Hydrogen Peroxide → HCID 58109203, compound

HRID 2037511Notes

Reaction equation

HRID 2037511 reaction equation
[CH2:1]([C@@:4]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].B1C2CCCC1CCC2.[OH-].[Na+].OO>C1COCC1>[F:26][C:20]1[CH:21]=[C:22]([F:25])[CH:23]=[CH:24][C:19]=1[C:16]1[CH:17]=[CH:18][C:13]([C@@H:11]([N:7]2[CH2:6][CH2:5][C@@:4]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)([CH2:1][CH2:2][CH3:3])[O:9][C:8]2=[O:10])[CH3:12])=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 58109303HCID 58109303, compound

Product 1

HCID 58109203HCID 58109203, compoundYield 36.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-6-allyl-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-phenyl-1,3-oxazinan-2-one (0.2475 g, 0.57 mmol, 1.0 equiv) in 6 mL of dry THF was added 9-BBN (0.5 M solution in THF, 2.3 mL, 1.15 mmol, 2.0 equiv). The mixture was stirred for 3 h at rt. It was then subjected to oxidative workup by adding 3 N aqueous NaOH (6 mL) followed by careful and dropwise addition of 50% aq H2O2 (4 mL) with vigorous stirring. The reaction mixture was stirred for 1 h, extracted with CH2Cl2, and dried over Na2SO4. Surprisingly, the reductive product was observed instead of hydroboration-oxidation. After the solvent was evaporated under reduced pressure, the residue was purified by reversed-phase HPLC (SunFire™ Prep C18 OBD™ 5 μm 19×50 mm column, 10%→90% CH3CN/H2O, 0.1% CF3COOH over 8 min and then 90% CH3CN/H2O, 0.1% CF3COOH over 2 min, flow rate 20 mL/min) to afford 0.0902 g of (R)-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-phenyl-6-propyl-1,3-oxazinan-2-one LC-MS Method 1 tR=2.22, min, m/z=436; 1H NMR (400 MHz, CD3OD) δ 7.33-7.14 (m, 8H), 6.96-6.87 (m, 4H), 5.48 (q, J=7.0 Hz, 1H), 3.01-2.96 (m, 1H), 2.41-2.36 (m, 1H), 2.29-2.21 (m, 1H), 2.14-2.07 (m, 1H), 1.81-1.72 (m, 2H), 1.46 (d, J=7.0 Hz, 3H), 1.39-1.29 (m, 1H), 1.08-0.98 (m, 1H), 0.76 (t, J=7.5 Hz, 3H); 19F NMR (376 MHz, CD3OD) δ −113.79 (m), −115.77 (m).

Workup

  1. stirringThe reaction mixture was stirred for 1 h
  2. extractionextracted with CH2Cl2
  3. dry with materialdried over Na2SO4
  4. customAfter the solvent was evaporated under reduced pressure
  5. customthe residue was purified by reversed-phase HPLC (SunFire™ Prep C18 OBD™ 5 μm 19×50 mm column, 10%
  6. customover 8 min
  7. wait90% CH3CN/H2O, 0.1% CF3COOH over 2 min

Sources & evidence

ORD record
ord-0af6c5c618594a22a16ba4ff5c39b959
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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