2,2'-Bipyridine → 6-(2-Hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one

HRID 1640825Notes

Reaction equation

HRID 1640825 reaction equation
[C:1]1([CH:7]2[O:12]C(=O)NC[CH2:8]2)C=CC=CC=1.[CH:14]1[CH:15]=CN=[C:18]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][N:25]=2)[CH:19]=1.[CH:26]1(B(O)O)CC1.[C:32]([O-:35])([O-])=[O:33].[Na+].[Na+]>ClC(Cl)C.CC([O-])=O.CC([O-])=O.[Cu+2]>[OH:12][C:7]([CH3:1])([CH3:8])[CH2:26][C:22]1([C:21]2[CH:15]=[CH:14][CH:19]=[CH:18][CH:20]=2)[O:35][C:32](=[O:33])[NH:25][CH2:24][CH2:23]1

Participants

7

Reactant 4

HCID 14742,2'-BipyridineHCID 10340Sodium CarbonateHCID 2410056-Phenyl-1,3-oxazinan-2-oneHCID 2760897Cyclopropylboronic acid

Product 1

HCID 866497576-(2-Hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of (S)-6-(2-hydroxy-2-methylpropyl)-3-(S)-1-(4-(2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one (1.683 g, 3.77 mmol, 1.0 equiv), Cu(OAc)2 (0.692 g, 3.81 mmol, 1.01 equiv), bipyridine (0.599 g, 3.83 mmol, 1.02 equiv), cyclopropylboronic acid (0.681 g, 7.93 mmol, 2.10 equiv) and Na2CO3 (0.890 g, 8.40 mmol, 2.23 equiv) in dichloroethane (40 mL) was stirred at 70° C. for 22 h under air. The reaction mixture was quenched with satd aq NH4Cl, diluted with CH2Cl2, dried over Na2SO4. After the solvent was removed under reduced pressure, the residue was purified by chromatography on silica gel eluted with MeOH/CH2Cl2 to afford 1.560 g (85%) of (S)-3-(S)-1-(4-(1-cyclopropyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one. LC-MS tR=1.41 min in 3 min chromatography, m/z 429, 487 (MH+); 1H NMR (400 MHz, CD3OD) δ 7.52 (d, J=7.0 Hz, 1H), 7.29-7.18 (m, 7H), 6.92 (d, J=8.2 Hz, 2H), 6.54 (d, J=1.8 Hz, 1H), 6.47 (dd, J=7.3, 1.8 Hz, 1H), 5.47 (q, J=7.0 Hz, 1H), 3.27-3.21 (m, 1H), 2.95-2.91 (m, 1H), 2.48-2.33 (m, 2H), 2.15-2.08 (m, 1H), 2.07 (s, 2H), 1.42 (d, J=7.0 Hz, 3H), 1.20 (s, 3H), 1.05-1.00 (m, 2H), 0.87 (s, 3H), 0.83-0.79 (m, 2H); 13C NMR (100 MHz, CD3OD) δ 166.17, 155.63, 152.88, 144.03, 142.27, 138.90, 136.91, 129.71, 128.70, 128.58, 127.67, 126.09, 116.08, 107.10, 85.19, 71.49, 55.13, 54.62, 37.44, 33.24, 32.71, 31.86, 30.03, 15.60, 7.27. (S)-3-((S)-1-(4-(1-cyclopropyl -2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl -1,3-oxazinan-2-one (ca. 1.5 g) and isopropyl acetate (30 mL) was heated in a 120° C. oil bath, affording a homogeneous solution. Heating was discontinued and the resulting solution was slowly stirred while slowly cooling to rt in the oil bath overnight. The solids were filtered and washed with isopropyl acetate, dried at room temperature under high vacuum affording crystalline solid Mp 91-94° C.

Workup

  1. customThe reaction mixture was quenched with satd aq NH4Cl
  2. additiondiluted with CH2Cl2
  3. dry with materialdried over Na2SO4
  4. customAfter the solvent was removed under reduced pressure
  5. customthe residue was purified by chromatography on silica gel
  6. washeluted with MeOH/CH2Cl2

Sources & evidence

ORD record
ord-b080856bfc3341dba5e36d4f12d921c1
Source dataset
uspto-grants-2012_02
Patent number
US08114868B2

Reaction notes

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