Ethyl Acetate → HCID 59635813, compound

HRID 1187941Notes

Reaction equation

HRID 1187941 reaction equation
[OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1.Br[C:37]1[CH:38]=[CH:39][C:40](=[O:46])[N:41]([CH2:43][CH2:44][F:45])[CH:42]=1.C([O-])([O-])=O.[Cs+].[Cs+].CCOC(C)=O>O1CCOCC1.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.O>[F:45][CH2:44][CH2:43][N:41]1[C:40](=[O:46])[CH:39]=[CH:38][C:37]([C:16]2[CH:15]=[CH:14][C:13]([C@@H:11]([N:7]3[CH2:6][CH2:5][C@:4]([CH2:3][C:2]([OH:1])([CH3:34])[CH3:35])([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[O:9][C:8]3=[O:10])[CH3:12])=[CH:18][CH:17]=2)=[CH:42]1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 59532385(S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-oneHCID 596357565-Bromo-1-(2-fluoroethyl)pyridin-2(1H)-one

Product 1

HCID 59635813HCID 59635813, compoundYield 20.8%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one (20 mg, 0.041 mmol), 5-bromo-1-(2-fluoroethyl)pyridin-2(1H)-one (9.2 mg, 0.041 mmol), and Cs2CO3 (2 N, 0.2 mL, 0.41 mmol) in 1,4-dioxane (2 mL) was added Pd(PPh3)2Cl2 (3 mg, 0.0041 mmol) under N2. The mixture was refluxed for 2 h, treated with EtOAc (10 mL) and water (10 mL). The organic layer was dried over Na2SO4, concentrated, and purified by preparative HPLC to give (S)-3-((S)-1-(4-(1-(2-fluoroethyl)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one (4.20 mg, 20%). LC-MS Method 2 tR=1.01 min, m/z=515, 493; 1H NMR (CD3OD): δ 0.97 (s, 3H), 1.28 (s, 3H), 1.56 (d, 3H), 2.18 (s, 2H), 2.22 (m, 1H), 2.49 (m, 2H), 3.05 (m, 1H), 4.37 (t, 1H), 4.43 (t, 1H), 4.69 (t, 1H), 4.81 (t, 1H), 5.59 (q, 1H), 6.66 (d, 1H), 7.05 (d, 2H), 7.33 (m, 7H), 7.82 (m, 2H).

Workup

  1. temperatureThe mixture was refluxed for 2 h
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-cc44e7a8d3324f8bad26ecbc278e2c58
Source dataset
uspto-grants-2014_03
Patent number
US08673899B2

Reaction notes

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