2,6-Difluoropyridine → HCID 58981715, compound
Reaction equation
[NH2:1][CH2:2][C@@H:3]([C@@H:5]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:6][CH2:7][CH2:8][CH3:9])[OH:4].NC[C@H]([C@@H](NC(=O)OC(C)(C)C)CCCC)O.C(N(CC)C(C)C)(C)C.[F:44][C:45]1[CH:50]=[CH:49][CH:48]=[C:47](F)[N:46]=1>O1CCOCC1.C(OCC)(=O)C>[F:44][C:45]1[N:46]=[C:47]([NH:1][CH2:2][C@@H:3]([C@@H:5]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:6][CH2:7][CH2:8][CH3:9])[OH:4])[CH:48]=[CH:49][CH:50]=1Participants
Conditions
- Temperature
- 45 °C
Procedure
To a solution of 100 mg (0.41 mmol) of tert-butyl (1S)-1-[(1S)-2-amino-1-hydroxyethyl]pentylcarbamate & tert-butyl (1S)-1-[(1R)-2-amino-1-hydroxyethyl]pentylcarbamate and 0.07 mL (0.46 mmol) of N,N-diisopropylethylamine in 0.5 mL dioxane was added 0.042 mL (0.46 mmol) of 2,6-difluoropyridine. The reaction mixture was stirred at 45° C. for 16 h, then at 50° C. for 20 h. The reaction mixture was then allowed to cool before being diluted with ethyl acetate, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with ethyl acetate:hexanes (3:7) to afford 40 mg (29%) of tert-butyl (1S)-1-{(1S)-2-[(6-fluoro-2-pyridinyl)amino]-1-hydroxyethyl}pentylcarbamate & tert-butyl (1S)-1-{(1R)-2-[(6-fluoro-2-pyridinyl)amino]-1-hydroxyethyl}pentylcarbamate. ES-LCMS m/z 364 (M+Na).
Workup
- waitat 50° C. for 20 h
- temperatureto cool
- washwashed with brine
- dry with materialdried over anhydrous magnesium sulfate
- concentrationconcentrated under reduced pressure
- customThe residue was purified by silica gel chromatography
- washeluting with ethyl acetate:hexanes (3:7)
Sources & evidence
- ORD record
- ord-9786c490d20242b69f5453494d1ccd10
- Source dataset
- uspto-grants-2007_10
- Patent number
- US07288541B2
Reaction notes
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