Sodium hydride → 5(S)-Isoxazol-3-ylaminomethyl-3-(3-fluoro-4-(3,6-dihydro-(2H)-pyran-4-yl)phenyl)oxazolidin-2-one
Reaction equation
ClC(Cl)(Cl)CO[C:5]([NH:7][C:8]1[CH:12]=[CH:11][O:10][N:9]=1)=O.[H-].[Na+].CS(OC[C@@H:23]1[O:27][C:26](=[O:28])[N:25]([C:29]2[CH:34]=[CH:33][C:32]([C:35]3[CH2:36][CH2:37][O:38][CH2:39][CH:40]=3)=[C:31]([F:41])[CH:30]=2)[CH2:24]1)(=O)=O>CN(C)C=O.CCCCCC>[O:10]1[CH:11]=[CH:12][C:8]([NH:7][CH2:5][C@@H:23]2[O:27][C:26](=[O:28])[N:25]([C:29]3[CH:34]=[CH:33][C:32]([C:35]4[CH2:36][CH2:37][O:38][CH2:39][CH:40]=4)=[C:31]([F:41])[CH:30]=3)[CH2:24]2)=[N:9]1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 55 °C
Procedure
To a stirred solution of 3-(2,2,2-trichloroethyloxycarbonylamino)isoxazole (631 mg, 2.43 mmol) in dry N,N-dimethylformamide (10 ml), under a nitrogen atmosphere was added a suspension of sodium hydride (107 mg of a 60% dispersion in oil, 2.67mmol) in hexane followed by 5(R)-methanesulfonyloxymethyl-3-(3-fluoro-4-(3,6-dihydro-(2H)-pyran-4-yl)phenyl)oxazolidin-2-one (see WO 97/09328; 226 mg, 0.61 mmol) in dry DMF (3 ml). Over a period of 24 hours further batches of sodium hydride totalling (428 mg of a 60% dispersion in oil, 10.7 mmol), were added and the reaction mixture heated to 50-60° C. for 24 h, after which time TLC indicated the formation, of the desired product (Rf 0.34, 50% ethyl acetate/hexane). The majority of the N,N-dimethylformamide was evaporated under hi-vacuum and the product isolated by MPLC (50%THF/Hexane) and then triturated with ether to yield the title compound as a white amorphous solid (63.4 mg, 29%). NMR: 2.42 (m, 2H), 3.45 (m, 2H), 3.81 (m, 3H), 4.15 (t, 1H), 4.21 (d, 2H), 4.90 (m, 1H), 6.01 (d, 1H), 6.09 (m, 1H), 6.53 (t, 1H), 7.31 (dd, 1H), 7.40 (t, 1H), 7.48 (dd, 1H), 8.39 (d, 1H); m/z: ES+ (M+H)=360.
Sources & evidence
- ORD record
- ord-4c39f18694ac4ef6bdf03fcd03f69976
- Source dataset
- uspto-grants-2004_05
- Patent number
- US06734200B1
Reaction notes
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