Sodium hydride → HCID 58109266, compound

HRID 2037424Notes

Reaction equation

HRID 2037424 reaction equation
OC(C1C=CC=CC=1)(C)[CH2:3][CH2:4][N:5]([C@H:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH3:14])[C:6](=[O:12])[O:7][C:8](C)(C)[CH3:9].[H-].[Na+]>C1COCC1>[CH3:9][C:8]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[O:7][C:6](=[O:12])[N:5]([C@H:13]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH3:14])[CH2:4][CH2:3]1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 58109295HCID 58109295, compound

Product 1

HCID 58109266HCID 58109266, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of crude tert-butyl 3-hydroxy-3-phenylbutyl((S)-1-phenylethyl)carbamate, obtained as described above, 60% NaH in oil (0.320 g) and THF (5 mL) was heated to reflux for 21 h. The reaction was then quenched with H2O (1.5 mL) and diluted with CH2Cl2. The organic layer was dried over Na2SO4. After the solvents were evaporated, the residue was purified by reversed-phase HPLC to afford 6-methyl-6-phenyl-3-((S)-1-phenylethyl)-1,3-oxazinan-2-one. After the solvents were evaporated, the residue was purified by reversed-phase HPLC (Phenomenex® Luna 5μ C18(2) 100 A, 250×21.20 mm, 5 micron, 10%→90% CH3CN/H2O, 0.1% CF3COOH over 13 min and then 90% CH3CN/H2O, 0.1% CF3COOH over 4 min, flow rate 25 mL/min) to afford 6-methyl-6-phenyl-3-((S)-1-phenylethyl)-1,3-oxazinan-2-one as a mixture of diastereomers. LC-MS Method 1 tR=1.71, 1.75 min, m/z=296 (MW); 1H NMR (400 MHz, CD3OD) δ 7.36-7.18 (m), 7.06-7.02 (m), 6.89-6.85 (m), 5.54 (q, J=7.1 Hz), 5.47 (q, J=7.0 Hz), 3.00-2.95 (m), 2.73-2.69 (m), 2.40-2.34 (m), 2.26-2.19 (m), 2.13-2.05 (m), 2.00-1.92 (m), 1.53 (s), 1.52 (s), 1.45 (d, J=7.0 Hz), 1.23 (d, J=7.0 Hz). A fraction containing on the less polar diastereomer was also isolated (Isomer 1). LC-MS Method 1 tR=1.75 min, m/z=296 (MH+); 1H NMR (400 MHz, CD3OD) δ 7.35-7.18 (m, 10H), 5.54 (q, J=7.0 Hz, 1H), 2.72-2.69 (m, 2H), 2.39-2.33 (m, 1H), 1.99-1.92 (m, 1H), 1.52 (s, 3H), 1.23 (d, J=7.0 Hz, 3H).

Workup

  1. customobtained
  2. temperaturewas heated
  3. temperatureto reflux for 21 h
  4. customThe reaction was then quenched with H2O (1.5 mL)
  5. additiondiluted with CH2Cl2
  6. dry with materialThe organic layer was dried over Na2SO4
  7. customAfter the solvents were evaporated
  8. customthe residue was purified by reversed-phase HPLC

Sources & evidence

ORD record
ord-4982462dfd6647758a6af6a0bd384673
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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