HCID 58109558, compound → HCID 59635765, compound

HRID 2037448Notes

Reaction equation

HRID 2037448 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([N:17]2[CH2:22][CH2:21][C@@:20]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)([CH2:23][C:24](=[O:26])[CH3:25])[O:19][C:18]2=[O:34])[CH3:16])=[CH:11][CH:10]=1.[CH3:35][Mg+].[Br-]>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([N:17]2[CH2:22][CH2:21][C@@:20]([C:27]3[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=3)([CH2:23][C:24]([OH:26])([CH3:35])[CH3:25])[O:19][C:18]2=[O:34])[CH3:16])=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 58109558HCID 58109558, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 59635765HCID 59635765, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (S)-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-(4-fluorophenyl)-6-(2-oxopropyl)-1,3-oxazinan-2-one (0.0303 g, 0.0648 mmol) in THF (5 mL) was added MeMgBr (1.4 M in toluene/THF, 1 mL, 1.4 mmol) at 0° C. The mixture was warmed to it and stirred for 1 h before quenching with satd aq NH4Cl (1 mL). The mixture was diluted with CH2Cl2 and dried over Na2SO4. After the solvent was evaporated under reduced pressure, the residue was purified by preparative 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 (S)-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-(4-fluorophenyl)-6-(2-hydroxy-2-methylpropyl)-1,3-oxazinan-2-one. LC-MS Method 1 tR=1.91 min, m/z 484 (MH+), 426; 1H NMR (400 MHz, CD3OD) δ 7.36-7.20 (m, 5H), 7.02-6.92 (m, 6H), 5.52 (q, J=7.0 Hz, 1H), 3.05-3.00 (m, 1H), 2.49-2.35 (m, 2H), 2.22-2.15 (m, 1H), 2.06 (s, 2H), 1.48 (d, J=7.0 Hz, 3H), 1.19 (s, 3H), 0.90 (s, 3H); 19F NMR (376 MHz, CD3OD) δ −113.78 (m), −115.82 (m), −117.50 (m).

Workup

  1. temperatureThe mixture was warmed to it
  2. custombefore quenching with satd aq NH4Cl (1 mL)
  3. additionThe mixture was diluted with CH2Cl2
  4. dry with materialdried over Na2SO4
  5. customAfter the solvent was evaporated under reduced pressure
  6. customthe residue was purified by preparative HPLC (SunFire™ Prep C18 OBD™ 5 μm 19×50 mm column, 10%
  7. customover 8 min
  8. wait90% CH3CN/H2O, 0.1% CF3COOH over 2 min

Sources & evidence

ORD record
ord-2d5846e10b16464ab9e8a543de390610
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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