Phosphorus oxychloride → HCID 59598981, compound
Reaction equation
[CH2:1]([N:4]1[C:12]2[C:11](=O)[NH:10][C:9]([NH2:14])=[N:8][C:7]=2[N:6]([C@@H:15]2[O:27][C@H:26]([CH2:28][O:29][C:30](=[O:32])[CH3:31])[C@@H:21]([O:22][C:23](=[O:25])[CH3:24])[C@H:16]2[O:17][C:18](=[O:20])[CH3:19])[C:5]1=[O:33])[CH:2]=[CH2:3].P(Cl)(Cl)([Cl:36])=O>>[CH2:1]([N:4]1[C:12]2[C:7](=[N:8][C:9]([NH2:14])=[N:10][C:11]=2[Cl:36])[N:6]([C@@H:15]2[O:27][C@H:26]([CH2:28][O:29][C:30](=[O:32])[CH3:31])[C@@H:21]([O:22][C:23](=[O:25])[CH3:24])[C@H:16]2[O:17][C:18](=[O:20])[CH3:19])[C:5]1=[O:33])[CH:2]=[CH2:3]Participants
Conditions
- Temperature
- 75 °C
Procedure
Compound 40 (0.65 g, 1.39 mmol) was dissolved in phosphorus oxychloride (10 mL) and heated to 75° C. for 16 h. The reaction mixture was concentrated under vacuum and the crude product dissolved in DCM. The mixture was then washed with NaHCO3 solution, brine, dried (MgSO4) and filtered. The filtrate was concentrated under vacuum and purified by flash chromatography using 10 to 50% gradient of ethyl acetate in hexanes. Removal of the solvent afforded 280 mg (41%) of the desired product 41: 1H NMR (400 MHz, CDCl3) δ 6.04 (d, J=4.0 Hz, 1H), 6.03 (t, J=5.6 Hz, 1H), 5.87 (m, 1H), 5.86 (t, J=5.6 Hz, 1H), 5.18 (m, 4H), 4.59 (d, J=8.0 Hz, 2H), 4.45 (d, J=7.6 Hz, 1H), 4.31 (m, 2H), 2.10 (s, 3H), 2.08 (s, 3H), 2.04 (s, 3H); MS (+)-ES [M+H]+ 484.2 m/z.
Workup
- concentrationThe reaction mixture was concentrated under vacuum
- dissolutionthe crude product dissolved in DCM
- washThe mixture was then washed with NaHCO3 solution, brine
- dry with materialdried (MgSO4)
- filtrationfiltered
- concentrationThe filtrate was concentrated under vacuum
- custompurified by flash chromatography
- customRemoval of the solvent
Sources & evidence
- ORD record
- ord-fff4627438df4a7fa3e80ac1a9c95629
- Source dataset
- uspto-grants-2012_07
- Patent number
- US08211863B2
Reaction notes
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