1,8-Diazabicyclo(5.4.0)undec-7-ene → 6-Allyl-6-(4-fluorophenyl)-3-((1-phenylpiperidin-4-yl)methyl)-1,3-oxazinan-2-one

HRID 2037459Notes

Reaction equation

HRID 2037459 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:28])([CH2:25][CH:26]=[CH2:27])[CH2:9][CH2:10][NH:11][CH2:12][CH:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:15][CH2:14]2)=[CH:4][CH:3]=1.Cl[C:30](Cl)([O:32]C(=O)OC(Cl)(Cl)Cl)Cl.C1CCN2C(=NCCC2)CC1>C1COCC1.N1C=CC=CC=1>[CH2:25]([C:8]1([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[O:28][C:30](=[O:32])[N:11]([CH2:12][CH:13]2[CH2:14][CH2:15][N:16]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:17][CH2:18]2)[CH2:10][CH2:9]1)[CH:26]=[CH2:27]

Participants

6

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 94429TriphosgeneHCID 581094683-(4-Fluorophenyl)-1-((1-phenylpiperidin-4-yl)methylamino)hex-5-en-3-ol

Product 1

HCID 581096806-Allyl-6-(4-fluorophenyl)-3-((1-phenylpiperidin-4-yl)methyl)-1,3-oxazinan-2-oneYield 20.6%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

3-(4-fluorophenyl)-1-((1-phenylpiperidin-4-yl)methylamino)hex-5-en-3-ol (120 mg, 0.314 mmol) was dissolved in THF (30 mL) and pyridine (c.a. 500 μL, excess). A solution of triphosgene (60 mg, excess) in THF (5 mL) was added slowly in 4 batches. After stirring 4 h at rt, DBU (94 μL, 2 equiv.) was added and the mixture was heated to reflux for overnight. There was still a lot of starting material on LC-MS spectra. The mixture was concentrated, redissolved in EtOAc (40 mL), washed with 5% aq HCl (2×8 mL), brine (8 mL), and dried over Na2SO4. After filtration and concentration, the residue was purified by prep HPLC to afford 6-allyl-6-(4-fluorophenyl)-3-((1-phenylpiperidin-4-yl)methyl)-1,3-oxazinan-2-one (17 mg, 13%). LC-MS Method 1 tR=1.32 min, m/z=409 (M+1); 1H NMR (CD3OD) 7.62-7.53 (m, 4H), 7.39 (m, 2H), 7.13 (t, 2H), 5.67 (m, 1H), 5.04 (dd, 2H), 3.05 (m, 2H), 2.63 (d, 2H), 2.57 (d, 1H), 2.32 (m, 1H), 2.06 (m, 1H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for overnight
  3. concentrationThe mixture was concentrated
  4. dissolutionredissolved in EtOAc (40 mL)
  5. washwashed with 5% aq HCl (2×8 mL), brine (8 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtration and concentration
  8. customthe residue was purified by prep HPLC

Sources & evidence

ORD record
ord-e826cb92e5bb487dbb044437d59b5c25
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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