1,4-Dioxane → (4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[5-(5-chloro-2-methoxypyridin-3-yl)-2-(methylthio)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

HRID 531230Notes

Reaction equation

HRID 531230 reaction equation
O1CCOCC1.[F:7][C:8]([F:45])([F:44])[C:9]1[CH:10]=[C:11]([C@H:19]2[O:23][C:22](=[O:24])[N:21]([CH2:25][C:26]3[C:31](B4OC(C)(C)C(C)(C)O4)=[CH:30][N:29]=[C:28]([S:41][CH3:42])[N:27]=3)[C@H:20]2[CH3:43])[CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1.Br[C:47]1[C:48]([O:54][CH3:55])=[N:49][CH:50]=[C:51]([Cl:53])[CH:52]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(#N)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:17][C:15]([F:16])([F:18])[C:13]1[CH:12]=[C:11]([C@H:19]2[O:23][C:22](=[O:24])[N:21]([CH2:25][C:26]3[C:31]([C:47]4[C:48]([O:54][CH3:55])=[N:49][CH:50]=[C:51]([Cl:53])[CH:52]=4)=[CH:30][N:29]=[C:28]([S:41][CH3:42])[N:27]=3)[C@H:20]2[CH3:43])[CH:10]=[C:9]([C:8]([F:7])([F:44])[F:45])[CH:14]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 135677513-Bromo-5-chloro-2-methoxypyridineHCID 90009110(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-{[2-(methylsulfanyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-4-yl]methyl}-1,3-oxazolidin-2-one2×

Product 1

HCID 118021383(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[5-(5-chloro-2-methoxypyridin-3-yl)-2-(methylthio)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
170 °C

Procedure

A dioxane (17.3 mL) solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-{[2-(methylsulfanyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-4-yl]methyl}-1,3-oxazolidin-2-one (INTERMEDIATE 21, 2.0 g, 3.46 mmol), 3-bromo-5-chloro-2-methoxypyridine (0.925 g, 4.16 mmol) and 2M potassium phosphate tribasic (3.5 mL, 7.00 mmol) in a microwave vial was evacuated and charged three times with nitrogen. Then Pd(Ph3P)4 (0.400 g, 0.346 mmol) was added and the reaction vial was capped. The reaction was stirred for 10 minutes at 170° C. in a microwave reactor. LCMS showed complete conversion to the product. The reaction was diluted with acetonitrile (5 mL) and filtered through a 2 g plug of RP C18 silica, rinsing with 10 mL acetonitrile. The filtrate was concentrated and the crude was purified by silica gel chromatography, eluting with a gradient of 0-50% ethyl acetate/hexanes to give the title compound as a pale yellow foam. LCMS (M+H)+: 593.3

Workup

  1. additioncharged three times with nitrogen
  2. customthe reaction vial was capped
  3. filtrationfiltered through a 2 g plug of RP C18 silica
  4. washrinsing with 10 mL acetonitrile
  5. concentrationThe filtrate was concentrated
  6. customthe crude was purified by silica gel chromatography
  7. washeluting with a gradient of 0-50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-6c437d4075684bf6bea1585d2eed4564
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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