Water → (R)-4-(6-((4-tert-butylcyclohexyl)methyl)naphthalen-2-yl)-4-methyloxazolidin-2-one

HRID 2389107Notes

Reaction equation

HRID 2389107 reaction equation
[C:1]([CH:5]1[CH2:10][CH2:9][CH:8]([CH2:11][B-](F)(F)F)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[K+].ClCCl.FC(F)(F)S(O[C:26]1[CH:35]=[CH:34][C:33]2[C:28](=[CH:29][CH:30]=[C:31]([C@:36]3([CH3:42])[CH2:40][O:39][C:38](=[O:41])[NH:37]3)[CH:32]=2)[CH:27]=1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1.O>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([CH:5]1[CH2:10][CH2:9][CH:8]([CH2:11][C:26]2[CH:27]=[C:28]3[C:33](=[CH:34][CH:35]=2)[CH:32]=[C:31]([C@:36]2([CH3:42])[CH2:40][O:39][C:38](=[O:41])[NH:37]2)[CH:30]=[CH:29]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 6

HCID 962WaterHCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 86642894(R)-6-(4-methyl-2-oxooxazolidin-4-yl)naphthalen-2-yl trifluoromethanesulfonateHCID 87390053Potassium 4-tert-butylcyclohexylmethyltrifluoroborate

Product 1

HCID 67415438(R)-4-(6-((4-tert-butylcyclohexyl)methyl)naphthalen-2-yl)-4-methyloxazolidin-2-oneYield 12.8%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A solution of potassium 4-tert-butylcyclohexylmethyltrifluoroborate (100 mg, 0.0004 mol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (31.4 mg, 0.0000384 mol), (R)-6-(4-methyl-2-oxooxazolidin-4-yl)naphthalen-2-yl trifluoromethanesulfonate (144 mg, 0.000384 mol) and cesium carbonate (0.376 g, 0.00115 mol) in 1,4-dioxane (4.6 mL, 0.059 mol) and water (0.5 mL, 0.03 mol) was heated at reflux under a nitrogen atmosphere. The reaction mixture was stirred at 100° C. overnight, then cooled to room temperature, and diluted with EtOAc, filtrate, followed by extraction of ether. The organic layers were combined and dried over MgSO4, and filtered. The concentrated residue was chromatographed with silica gel under 0-100% EtOAc/hexane to give (R)-4-(6-((4-tert-butylcyclohexyl)methyl)naphthalen-2-yl)-4-methyloxazolidin-2-one as a solid (18.6 mg, 12.8%). 1H NMR (400 MHz, CHLOROFORM-d) δ=7.84 (d, J=8.7 Hz, 1 H), 7.79 (br. s., 1 H), 7.77 (d, J=8.5 Hz, 1 H), 7.60 (s, 1 H), 7.45 (dd, J=1.9, 8.6 Hz, 1 H), 7.38 (d, J=8.4 Hz, 1 H), 5.83 (br. s., 1 H), 4.46-4.39 (m, 2 H), 2.82 (d, J=7.9 Hz, 2 H), 2.09 (m., 1 H), 1.87 (s, 3 H), 1.68-1.40 (m, 5 H), 1.39-1.24 (m, 2 H), 1.08-0.96 (m, 1 H), 0.91 (s, 9 H).

Workup

  1. temperatureat reflux under a nitrogen atmosphere
  2. temperaturecooled to room temperature
  3. extractionfollowed by extraction of ether
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customThe concentrated residue was chromatographed with silica gel under 0-100% EtOAc/hexane

Sources & evidence

ORD record
ord-6b7ac2ecbf6f445f93b7d583141d1317
Source dataset
uspto-grants-2012_09
Patent number
US08269043B2

Reaction notes

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