Methyl chloroformate → HCID 58758412, compound

HRID 459031Notes

Reaction equation

HRID 459031 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:21]2[CH2:25][C@H:24]([CH2:26][N:27]3[CH:31]=[CH:30][N:29]=[N:28]3)[O:23][C:22]2=[O:32])[CH:5]=[CH:6][C:7]=1[C:8]1[CH:9]=[N:10][C:11]([C:14]2[CH2:18][C@@H:17]([CH2:19][OH:20])[O:16][N:15]=2)=[CH:12][CH:13]=1.Cl[C:34]([O:36][CH3:37])=[O:35].ClC([O-])=O>CN(C=O)C.N1C=CC=CC=1.O>[C:34](=[O:35])([O:36][CH3:37])[O:20][CH2:19][C@H:17]1[O:16][N:15]=[C:14]([C:11]2[CH:12]=[CH:13][C:8]([C:7]3[CH:6]=[CH:5][C:4]([N:21]4[CH2:25][C@H:24]([CH2:26][N:27]5[CH:31]=[CH:30][N:29]=[N:28]5)[O:23][C:22]4=[O:32])=[CH:3][C:2]=3[F:1])=[CH:9][N:10]=2)[CH2:18]1

Participants

7

Reactant 3

HCID 6586Methyl chloroformate3×HCID 9932836(5R)-3-(3-Fluoro-4-{6-[(5S)-5-(hydroxymethyl)-4,5-dihydroisoxazol-3-yl]pyridin-3-yl}phenyl)-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-oneHCID 21226386Carbonochloridate

Product 1

HCID 58758412HCID 58758412, compoundYield 54.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(5R)-3-(3-Fluoro-4-{6-[(5S)-5-(hydroxymethyl)-4,5-dihydroisoxazol-3-yl]pyridin-3-yl}phenyl)-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one (Example 1, 0.2 g, 0.46 mmol) was dissolved in DMF (4 ml) and pyridine (1 ml), then cooled to 0° C. Methyl chloroformate (0.2 ml, 2.57 mmol) was added and the mixture was stirred for 45 minutes at 0° C. A further portion of methyl chloroformate was added (0.2 ml), and the mixture was stirred for a further 2 hours 15 minutes before addition of a third portion of methyl chloroformate (0.2 ml). The mixture was stirred for a further hour at 0° C. after the third chloroformate addition, then diluted with water, extracted twice with ethyl acetate and dried over sodium sulfate. The residue obtained upon filtration and evaporation was purified via chromatography (silica gel, 0 to 10% acetonitrile in ethyl acetate). Evaporation of the fractions containing product and trituration of the resulting solid with diethyl ether yielded the title compound as a white solid (0.125 g), melting point: 205° C.

Workup

  1. stirringThe mixture was stirred for a further hour at 0° C.
  2. extractionextracted twice with ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. customThe residue obtained upon filtration and evaporation
  5. customwas purified via chromatography (silica gel, 0 to 10% acetonitrile in ethyl acetate)
  6. customEvaporation of the fractions
  7. additioncontaining product and trituration of the resulting solid with diethyl ether

Sources & evidence

ORD record
ord-0f8615d8e4694fc9b860c510a4ae5dd5
Source dataset
uspto-grants-2007_03
Patent number
US07192974B2

Reaction notes

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