Triphenylphosphine → (4R,5R)-4-(2-fluoro-5-((trimethylsilyl)ethynyl)pyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one

HRID 2362364Notes

Reaction equation

HRID 2362364 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@@H:9]2[C@@H:13]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=3)[O:12][C:11](=[O:21])[NH:10]2)[C:5]([F:8])=[N:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:41]([Si:43]([CH3:46])([CH3:45])[CH3:44])#[CH:42]>[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(N(CC)CC)C>[F:8][C:5]1[C:4]([C@@H:9]2[C@@H:13]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=3)[O:12][C:11](=[O:21])[NH:10]2)=[CH:3][C:2]([C:42]#[C:41][Si:43]([CH3:46])([CH3:45])[CH3:44])=[CH:7][N:6]=1

Participants

7

Reactant 3

HCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 69083956(4R,5R)-4-(5-bromo-2-fluoropyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one

Product 1

HCID 69084079(4R,5R)-4-(2-fluoro-5-((trimethylsilyl)ethynyl)pyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-oneYield 69.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
90 °C

Procedure

To a sealable microwave vial was added (4R,5R)-4-(5-bromo-2-fluoropyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one (105 mg, 0.296 mmol), copper(I) iodide (1.689 mg, 8.87 μmol), triphenylphosphine (23.26 mg, 0.089 mmol) and triethylamine (4 mL). The solution was stirred and ethynyltrimethylsilane (43.6 mg, 0.443 mmol) was added and the reaction mixture was degassed with nitrogen for 10 min. To this mixture was added bis(triphenylphosphine)palladium(II) chloride (4.15 mg, 5.91 μmol) in one portion and the reaction vessel was sealed and heated to 90° C. overnight. The reaction was cooled to room temperature, the solvent was evaporated in vacuo and the crude solid was added to a silica gel column and eluted with 20% EtOAc/80% Hexanes affording (4R,5R)-4-(2-fluoro-5-((trimethylsilyl)ethynyl)pyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one (77 mg, 0.207 mmol, 69.9% yield) as an off white solid. 1H-NMR (CDCl3, 400 MHz) δ 8.35 (s, 1H), 8.04 (dd, J=8.0, 4.0, 1H), 7.47-7.41 (m, 1H), 7.18-7.12 (m, 3H), 5.44 (brs, 1H), 5.36 (d, J=4.0, 1H) 5.00 (d, J=5.0, 1H), 0.30 (s, 9H), LC/Mass spec. (Analytical HPLC method 2): RT=2.23 min. Mass=373.19 (MH)+.

Workup

  1. customthe reaction mixture was degassed with nitrogen for 10 min
  2. customthe reaction vessel was sealed
  3. temperatureThe reaction was cooled to room temperature
  4. customthe solvent was evaporated in vacuo
  5. additionthe crude solid was added to a silica gel column
  6. washeluted with 20% EtOAc/80% Hexanes

Sources & evidence

ORD record
ord-c8483c6f3c1643f7ab5c75d06a33ec7d
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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