Tetrahydrofuran → methyl {3-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-chloropyridin-3-yl]-4-methoxyphenyl}acetate

HRID 604672Notes

Reaction equation

HRID 604672 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25](Br)=[CH:24][CH:23]=[C:22]([Cl:27])[N:21]=3)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:31][O:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39][C:40]([O:42][CH3:43])=[O:41])=[CH:35][C:34]=1B1OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[K+].[K+].C1COCC1>CCOC(C)=O.[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:38]4[CH:37]=[C:36]([CH2:39][C:40]([O:42][CH3:43])=[O:41])[CH:35]=[CH:34][C:33]=4[O:32][CH3:31])=[CH:24][CH:23]=[C:22]([Cl:27])[N:21]=3)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 57576268(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-oneHCID 57576289Methyl 2-(4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)phenyl)acetate

Product 1

HCID 57576209methyl {3-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-chloropyridin-3-yl]-4-methoxyphenyl}acetate

Reagents, catalysts & solvents 2

HCID 178454861HCID 178454861, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A flask was charged with (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one (265 mg, 0.511 mmol), methyl [4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetate (156.6 mg, 0.511 mmol), 1M K2CO3 (4 mL, 4 mmol), and THF (4 mL). The reaction was degassed with N2 and then 1,1′-bis(di-t-butylphosphino)ferrocene palladium dichloride (16.7 mg, 0.026 mmol) was added while the reaction was stirred vigorously. Vigorous stirring was continued for 15 min at room temperature, and then the reaction was diluted with EtOAc (40 mL) and washed with water and brine (20 mL each). The organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash chromatography on silica gel (0 to 70% EtOAc/hexanes) to afford methyl {3-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-chloropyridin-3-yl]-4-methoxyphenyl}acetate. Rf=0.21 (25% EtOAc/hexanes). LCMS=617.4 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 6.92-7.83 (m, 8H), 4.88-5.68 (m, 2H), 3.58-4.19 (m, 10H), 0.63 (s, 3H).

Workup

  1. customThe reaction was degassed with N2
  2. stirringVigorous stirring
  3. washwashed with water and brine (20 mL each)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography on silica gel (0 to 70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-a24322568b8e42fd9c2393683487e582
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

Loading…