Tricyclohexylphosphine → [4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfanyl)pyrimidin-5-yl]boronic acid

HRID 1508534Notes

Reaction equation

HRID 1508534 reaction equation
[F:1][C:2]([F:31])([F:30])[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][N:23]=[C:22]([S:27][CH3:28])[N:21]=3)[C@H:14]2[CH3:29])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[B:32]1(B2OC(C)(C)CC(C)O2)[O:37]C(C)(C)CC(C)[O:33]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C([O-])(=O)C.[K+]>C1COCC1>[F:1][C:2]([F:31])([F:30])[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]([B:32]([OH:37])[OH:33])=[CH:24][N:23]=[C:22]([S:27][CH3:28])[N:21]=3)[C@H:14]2[CH3:29])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 4

HCID 75806TricyclohexylphosphineHCID 517044Potassium AcetateHCID 2734616Bis(hexylene Glycolato)diboronHCID 57576287(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[5-bromo-2-(methylthio)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 86704623[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfanyl)pyrimidin-5-yl]boronic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5-bromo-2-(methylsulfanyl)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (400 mg, 0.754 mmol), bis(hexyleneglycolato)diboron (249 mg, 0.981 mmol), tricyclohexylphosphine (85 mg, 0.302 mmol), potassium acetate (163 mg, 1.659 mmol), 1,1bis(di-tert-butylphosphino)ferrocene palladium dichloride (51.3 mg, 0.075 mmol) and THF (10 mL) were sealed in a microwave vessel and subject to microwave irradiation at 140° C. for 60 min. LCMS indicated complete consumption of starting material and formation of the desired product. The resulting crude mixture was purified by flash chromatography (SiO2, Biotage SNAP Cartridge, silica gel, KP-Sil, 50 g cartridge). The column was eluted by an EtOAc/hexanes mixture (0% to 40%). Related fractions were evaporated into a brown solid foam as the titled compound. LCMS calc.=495.09. found=495.91 (M+H)+.

Workup

  1. customsubject to microwave irradiation at 140° C. for 60 min
  2. customconsumption of starting material and formation of the desired product
  3. customThe resulting crude mixture was purified by flash chromatography (SiO2, Biotage SNAP Cartridge, silica gel, KP-Sil, 50 g cartridge)
  4. washThe column was eluted by an EtOAc/hexanes mixture (0% to 40%)
  5. customRelated fractions were evaporated into a brown solid foam as the titled compound

Sources & evidence

ORD record
ord-cd8e506f4c7f4ad489c5e3fedee73cb5
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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