Methanol → HCID 58109237, compound

HRID 2037481Notes

Reaction equation

HRID 2037481 reaction equation
[CH2:1]([C@@:4]1([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([O:19]C)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].B(Br)(Br)Br.CO>C(Cl)Cl.[Cl-].[Na+].O>[CH2:1]([C@@:4]1([C:21]2[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 887MethanolHCID 25134Boron tribromide2×HCID 58109563HCID 58109563, compound

Product 1

HCID 58109237HCID 58109237, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of (R)-6-allyl-6-(4-fluorophenyl)-3-((S)-1-(4-methoxyphenyl)ethyl)-1,3-oxazinan-2-one (0.1094 g, 0.30 mmol, 1.0 equiv) in 6 mL of dry CH2Cl2 was cooled to −78° C. At this temperature, BBr3 (1.0 M solution in CH2Cl2, 0.6 mL, 0.60 mmol, 2.0 equiv) was added under N2 atmosphere. After 1 h, the reaction mixture was stirred at an ice bath for further 3 h. After the reaction mixture was cooled with a dry ice—acetone bath, surplus of BBr3 was hydrolyzed with methanol (3 mL). The mixture was then treated with brine, diluted with CH2Cl2, and dried over Na2SO4. 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 0.0669 g (64%) of (R)-6-allyl-6-(4-fluorophenyl)-3-((S)-1-(4-hydroxyphenyl)ethyl)-1,3-oxazinan-2-one. LC-MS Method 1 tR=1.57 min, m/z 356 (MH+); 1H NMR (400 MHz, CD3OD) δ 7.23-7.18 (m, 2H), 7.00-6.96 (m, 2H), 6.63 (d, J=8.8 Hz, 2H), 6.43 (d, J=8.2 Hz, 2H), 5.64-5.54 (m, 1H), 5.34 (q, J=7.0 Hz, 1H), 4.96-4.89 (m, 2H), 2.93-2.88 (m, 1H), 2.50 (d, J=7.0 Hz, 2H), 2.34-2.29 (m, 1H), 2.18-2.03 (m, 2H), 1.36 (d, J=7.0 Hz, 3H); 19F NMR (376 MHz, CD3OD) δ −117.48 (m).

Workup

  1. temperatureAfter the reaction mixture was cooled with a dry ice—acetone bath
  2. dry with materialdried over Na2SO4
  3. customAfter the solvent was evaporated under reduced pressure
  4. customthe residue was purified by reversed-phase HPLC (SunFire™ Prep C18 OBD™ 5 μm 19×50 mm column, 10%
  5. customover 8 min
  6. wait90% CH3CN/H2O, 0.1% CF3COOH over 2 min

Sources & evidence

ORD record
ord-bf7a72cb03dd485aa371d78f2cf24139
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

Loading…