Tetrabutylammonium Fluoride → (R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one

HRID 470467Notes

Reaction equation

HRID 470467 reaction equation
[Si]([O:8][CH2:9][CH2:10][CH2:11][C@@:12]1([C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=2)[O:17][C:16](=[O:18])[N:15]([C@H:19]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][C:30](=[O:33])[N:29]([CH3:34])[CH:28]=3)=[CH:23][CH:22]=2)[CH3:20])[CH2:14][CH2:13]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CC#N>[F:41][C:38]1[CH:39]=[CH:40][C:35]([C@:12]2([CH2:11][CH2:10][CH2:9][OH:8])[O:17][C:16](=[O:18])[N:15]([C@H:19]([C:21]3[CH:26]=[CH:25][C:24]([C:27]4[CH:32]=[CH:31][C:30](=[O:33])[N:29]([CH3:34])[CH:28]=4)=[CH:23][CH:22]=3)[CH3:20])[CH2:14][CH2:13]2)=[CH:36][CH:37]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 59635791(R)-6-(3-(tert-butyldimethylsilyloxy)propyl)-6-(4-fluorophenyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one

Product 1

HCID 59635723(R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-oneYield 4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of (R)-6-(3-(tert-butyldimethylsilyloxy)propyl)-6-(4-fluorophenyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one (200 mg, 0.35 mmol) and TBAF (182 mg, 0.7 mmol) in CH3CN was stirred and heated to reflux for 15 min. When the reaction was over, the mixture was washed with water and extracted with EtOAc. The combined organic phase was washed with brine, dried over Na2SO4, filtered and concentrated to give crude product, which was purified by preparative HPLC to give (R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-3-((S)-1-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one (5.01 mg, 4%). LC-MS Method 2 tR=1.065 min, m/z=464.21; 1H NMR (CDCl3): δ=1.38 (m, 1H), 1.47 (d, 3H), 1.63 (m, 2H), 1.91 (m, 2H), 2.10-2.30 (m, 3H), 2.87 (m, 1H), 2.84 (m, 1H), 3.51 (m, 2H), 3.56 (s, 3H), 5.63 (m, 1H), 6.67 (m, 1H), 6.87-6.98 (m, 4H), 7.15 (m, 2H), 7.27 (m, 1H), 7.29 (m, 1H), 7.32 (m, 1H), 7.55 (m, 1H).

Workup

  1. temperatureheated
  2. temperatureto reflux for 15 min
  3. washwas washed with water
  4. extractionextracted with EtOAc
  5. washThe combined organic phase was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give crude product, which
  10. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-104bbe5382b4452da68f79dd044de5ec
Source dataset
uspto-grants-2014_01
Patent number
US08629138B2

Reaction notes

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