Diethylamine → butyl 4-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-2,2-dimethylbut-3-ynoate

HRID 333895Notes

Reaction equation

HRID 333895 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@:13]([CH2:22][C:23]([OH:26])([CH3:25])[CH3:24])([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[O:12][C:11]2=[O:27])[CH3:9])=[CH:4][CH:3]=1.[CH3:28][C:29]([CH3:39])([C:37]#[CH:38])[C:30]([O:32][CH2:33][CH2:34][CH2:35][CH3:36])=[O:31].N(CC)CC>[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCN(CC)CC>[OH:26][C:23]([CH3:25])([CH3:24])[CH2:22][C@@:13]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[O:12][C:11](=[O:27])[N:10]([C@H:8]([C:5]2[CH:6]=[CH:7][C:2]([C:38]#[C:37][C:29]([CH3:28])([CH3:39])[C:30]([O:32][CH2:33][CH2:34][CH2:35][CH3:36])=[O:31])=[CH:3][CH:4]=2)[CH3:9])[CH2:15][CH2:14]1

Participants

7

Reactant 3

HCID 8021DiethylamineHCID 44599033(S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-oneHCID 86670540Butyl 2,2-dimethylbut-3-ynoate

Product 1

HCID 66869601butyl 4-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-2,2-dimethylbut-3-ynoateYield 19%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

A microwave vial was charged with (S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one (50 mg, 0.12 mmol), butyl 2,2-dimethylbut-3-ynoate (40 mg, 0.23 mmol), CuI (2.2 mg, 0.012 mmol), PdCl2(PPh3)2 (5 mg, 0.008 mmol), Et3N (2 mL) and Et2NH (0.2 mL). The mixture was sparged with N2 for 10 min and heated at 100 C for 2 h. The mixture was concentrated, redissolved in EtOAc (90 mL), washed with 5% aq HCl (20 mL) and brine (20 mL), and dried over Na2SO4. Removal of the solvent left an oil (75 mg) which was purified by prep HPLC to afford butyl 4-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-2,2-dimethylbut-3-ynoate (11 mg, 19%). LC-MS Method 1 tR=2.13 min, m/z=520, 462.

Workup

  1. customThe mixture was sparged with N2 for 10 min
  2. temperatureheated at 100 C for 2 h
  3. concentrationThe mixture was concentrated
  4. dissolutionredissolved in EtOAc (90 mL)
  5. washwashed with 5% aq HCl (20 mL) and brine (20 mL)
  6. dry with materialdried over Na2SO4
  7. customRemoval of the solvent
  8. waitleft an oil (75 mg) which
  9. customwas purified by prep HPLC

Sources & evidence

ORD record
ord-6cef5154ed044f349946c02c07e55479
Source dataset
uspto-grants-2014_11
Patent number
US08883778B2

Reaction notes

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