Cesium carbonate → (S)-3-((S)-3-(4-(4-Bromo-3-(trifluoromethoxy)benzyloxy)-phenyl)-3-(isoxazol-3-yl)propanoyl)-4-benzyloxazolidin-2-one

HRID 2235605Notes

Reaction equation

HRID 2235605 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][C:3]=1[O:10][C:11]([F:14])([F:13])[F:12].S(Br)(Br)=O.[CH2:19]([C@H:26]1[CH2:30][O:29][C:28](=[O:31])[N:27]1[C:32](=[O:47])[CH2:33][C@@H:34]([C:40]1[CH:45]=[CH:44][C:43](O)=[CH:42][CH:41]=1)[C:35]1[CH:39]=[CH:38][O:37][N:36]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][C:43]2[CH:42]=[CH:41][C:40]([C@@H:34]([C:35]3[CH:39]=[CH:38][O:37][N:36]=3)[CH2:33][C:32]([N:27]3[C@@H:26]([CH2:19][C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH2:30][O:29][C:28]3=[O:31])=[O:47])=[CH:45][CH:44]=2)=[CH:4][C:3]=1[O:10][C:11]([F:13])([F:12])[F:14]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 68176Thionyl bromideHCID 54472733(4-Bromo-3-(trifluoromethoxy)phenyl)methanolHCID 57801829(S)-4-Benzyl-3-((S)-3-(4-hydroxyphenyl)-3-(isoxazol-3-yl)propanoyl)oxazolidin-2-one

Product 1

HCID 59300650(S)-3-((S)-3-(4-(4-Bromo-3-(trifluoromethoxy)benzyloxy)-phenyl)-3-(isoxazol-3-yl)propanoyl)-4-benzyloxazolidin-2-one

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 28.3 (1.30 g, 4.80 mmol), thionyl bromide (1.01 g, 4.84 mmol), and DMF (0.1 mL) in DCM (8.0 mL) was stirred at room temperature for 50 minutes. The solvent was then removed. To the residue was added 7.5 (1.10 g, 2.80 mmol) and Cs2CO3 (1.10 g, 3.36 mmol) in DMF (8.0 mL). The mixture was stirred at room temperature for 4 hours. EtOAc (150 mL) was added, and the mixture was washed with brine (25×3 mL) and dried with MgSO4. The solvent was removed, and the crude product was purified by CombiFlash, eluting with EtOAc and hexane, to give the title compound 28.4. 1H NMR (CDCl3) δ 2.77 (dd, J=4.2, 9.5 Hz, 1H), 3.21 (dd, J=4.2, 9.5 Hz, 1H), 3.52 (dd, J=8.6, 17.6 Hz, 1H), 4.04 (dd, J=8.6, 17.6 Hz, 1H), 4.63 (m, 1H), 4.76 (m, 1H), 5.01 (s, 2H), 6.14 (d, J=1.5 Hz, 1H), 6.92 (d, J=6.9, Hz, 2H), 7.20-7.35 (m, 9H), 7.64 (d, J=8.3, Hz, 1H), 8.31 (d, J=1.5 Hz, 1H). MS ESI (pos.) m/e: 647 (M+H).

Workup

  1. customThe solvent was then removed
  2. stirringThe mixture was stirred at room temperature for 4 hours
  3. washthe mixture was washed with brine (25×3 mL)
  4. dry with materialdried with MgSO4
  5. customThe solvent was removed
  6. customthe crude product was purified by CombiFlash
  7. washeluting with EtOAc and hexane

Sources & evidence

ORD record
ord-f089181fa7a94b4a84a653d1a88ba779
Source dataset
uspto-grants-2010_05
Patent number
US07714008B2

Reaction notes

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