Triethylamine → Methyl 4-((4S,5R)-3-(2,2-dichloroacetyl)-4-(fluoro-methyl)-2,2-dimethyloxazolidin-5-yl)benzoate

HRID 1487445Notes

Reaction equation

HRID 1487445 reaction equation
[Cl:1][CH:2]([Cl:21])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15](I)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:20])[CH3:19])=[O:4].C(N(CC)CC)C.CC1(C)C2[C:51](=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:50][C:32]2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[C]=[O:72]>O.CC([O-])=O.CC([O-])=O.[Pd+2].CO>[Cl:1][CH:2]([Cl:21])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:32]([O:50][CH3:51])=[O:72])=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:20])[CH3:19])=[O:4]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86695394(4S,5R)-3-(dichloroacetyl)-4-(fluoromethyl)-5-(4-iodophenyl)-2,2-dimethyl-1,3-oxazolidineHCID 178418416HCID 178418416, compound

Product 1

HCID 86695393Methyl 4-((4S,5R)-3-(2,2-dichloroacetyl)-4-(fluoro-methyl)-2,2-dimethyloxazolidin-5-yl)benzoate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a flask containing 2,2-dichloro-1-((4S,5R)-4-(fluoromethyl)-5-(4-iodophenyl)-2,2-dimethyloxazolidin-3-yl)ethanone (2.0 g, 4.48 mmol) is added triethylamine (5 mL) and methanol (5 mL). Carbon monoxide gas is bubbled through the solution while stirring for 30 min. Pd(OAc)2 (51 mg, 0.22 mmol) and Xantphos (132 mg, 0.22 mmol) are next added and a balloon containing carbon monoxide is secured to the flask outlet. The reaction is heated for 2 hours at 60° C. and then cooled to room temperature. Next, the reaction is diluted with water, extracted with ethylacetate, dried over Na2SO4, and concentrated under vacuum. The residue is chromatographed on silica gel eluting from 100% hexanes to 50:50 ethylacetate:hexanes to afford the title compound (1.11 g): 1H NMR (400 MHz, CDCl3) 8.10 (d, 2H, J=8.0 Hz), 7.55 (d, 2H, J=8.0 Hz), 6.34 (m, 1H), 5.30-4.42 (m, 4H), 3.95 (s, 3H), 1.97-1.53 (m, 6H). m/z (CI) 320 [M-(CH3)2CO].

Workup

  1. customCarbon monoxide gas is bubbled through the solution
  2. temperaturecooled to room temperature
  3. extractionextracted with ethylacetate
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under vacuum
  6. customThe residue is chromatographed on silica gel eluting from 100% hexanes to 50:50 ethylacetate

Sources & evidence

ORD record
ord-7616ce6901824690bb5196d5945d06da
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

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