Nitrogen → HCID 88174277, compound
Reaction equation
[F:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[N:8]2)=[CH:4][CH:3]=1.N#N.[Li]CCCC.[F:25][CH:26]([P:28](=[O:48])([O-:47])[O:29][C:30]1[CH:35]=[C:34](C(C)(C)C)[C:33]([CH2:40]Br)=[C:32](C(C)(C)C)[C:31]=1[Br:46])[F:27]>C1COCC1>[N:7]1([CH:6]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:17][CH:16]=2)[CH2:40][C:33]2[CH:34]=[CH:35][C:30]([O:29][P:28]([CH:26]([F:27])[F:25])(=[O:47])[OH:48])=[C:31]([Br:46])[CH:32]=2)[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[N:8]1Participants
Conditions
- Temperature
- -78 °C
Procedure
A solution of 1-(4-fluorobenzyl)-1H-benzotriazole (91 mg) in THF (5 mL) at −78° C. was pumped under high vacuum for 5 min., then N2 was introduced in the reaction vessel. A solution of 0.98M n-BuLi in hexanes (0.41 mL) was then added, and the solution turned deep blue immediately. After stirring for 5 min at −78° C., a solution of (2-bromo-4-bromomethylphenyl)difluoromethylphosphonic acid di-tert-butyl ester (Example 1, Step 6)(157 mg) in THF (1.5 mL) was added. The deep blue color disappeared. The mixture was then stirred at −78° C. for 15 min then quenched with H2O and extracted with EtOAc. The EtOAc extract was washed with brine, dried (MgSO4) and concentrated. Chromatography over silica gel and elution with hexane:EtOAc (65:35, 0.2% Et3N), provided 85 mg of the intermediate.
Workup
- stirringThe mixture was then stirred at −78° C. for 15 min
- customthen quenched with H2O
- extractionextracted with EtOAc
- extractionThe EtOAc extract
- washwas washed with brine
- dry with materialdried (MgSO4)
- concentrationconcentrated
- washChromatography over silica gel and elution with hexane:EtOAc (65:35, 0.2% Et3N)
Sources & evidence
- ORD record
- ord-74fb5184257b4fd1a73f280442917c4c
- Source dataset
- uspto-grants-2002_11
- Patent number
- US06486142B2
Reaction notes
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