HCID 58109464, compound → HCID 58109537, compound

HRID 2037594Notes

Reaction equation

HRID 2037594 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@@:13]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)([CH2:16][C:17](=[O:19])[CH3:18])[O:12][C:11]2=[O:27])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[CH3:28][Mg+].[Br-]>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@@:13]([C:20]3[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=3)([CH2:16][C:17]([OH:19])([CH3:28])[CH3:18])[O:12][C:11]2=[O:27])[CH3:9])[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 58109464HCID 58109464, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 58109537HCID 58109537, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of (S)-3-((S)-1-(3-bromophenyl)ethyl)-6-(4-fluorophenyl)-6-(2-oxopropyl)-1,3-oxazinan-2-one (18.5 mg, 0.043 mmol) in dry toluene (3 mL) was cooled to 0° C. A solution of MeMgBr (3.0M in THF, 45 μL, 3 equiv) was added. After 15 min, the mixture was warmed to rt slowly and stirred 2 h. LC-MS found reaction completed. The reaction was quenched by satd aq NH4Cl solution (2 mL), diluted with EtOAc (10 mL), washed with 1% aq HCl (3 mL), brine (3 mL), and dried over Na2SO4. After filtration and concentration, the residue was purified by preparative HPLC to afford (S)-3-((S)-1-(3-bromophenyl)ethyl)-6-(4-fluorophenyl)-6-(2-hydroxy-2-methylpropyl)-1,3-oxazinan-2-one (8.0 mg, 42%). LC-MS (3 min) tR=1.75 min, m/z=472, 474 (M+Na); 1H NMR (CDCl3) 7.32-7.21 (m, 3H), 7.12-6.98 (m, 4H), 6.89 (m, 1H), 5.65 (q, 1H), 2.89 (m, 1H), 1.50 (d, 3H), 1.15 (d, 6H).

Workup

  1. customreaction
  2. customThe reaction was quenched by satd aq NH4Cl solution (2 mL)
  3. additiondiluted with EtOAc (10 mL)
  4. washwashed with 1% aq HCl (3 mL), brine (3 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationAfter filtration and concentration
  7. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-252a5817ae9f4428a9b157251b922080
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

Loading…