Pyridine → (9H-Fluoren-9-yl)methyl ((2S,3S)-1-fluoro-3-methyl-1-oxopentan-2-yl)carbamate
Reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@@H:19]([C@@H:23]([CH3:26])[CH2:24][CH3:25])[C:20](O)=[O:21])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.CCN(S(F)(F)[F:39])CC>C(Cl)Cl>[F:39][C:20](=[O:21])[C@@H:19]([NH:18][C:16](=[O:17])[O:15][CH2:14][CH:12]1[C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:5]2[C:13]1=[CH:1][CH:2]=[CH:3][CH:4]=2)[C@@H:23]([CH3:26])[CH2:24][CH3:25]Participants
Procedure
To a solution of (2S,3S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-methylpentanoic acid (Fmoc-Isoleucine) (7 g, 19.81 mmol) and pyridine (1.602 mL, 19.81 mmol) in DCM (120 mL) was added via cannula a solution of DAST (3.11 mL, 23.77 mmol) in DCM (20 mL) over 10 min. The reaction mixture was stirred at room temperature for 1 hour, diluted with DCM (80 mL), washed with ice-cold water (2×200 mL), the organic layer was dried over MgSO4, filtered, and evaporated in vacuo to give (9H-fluoren-9-yl)methyl (2S,3S)-1-fluoro-3-methyl-1-oxopentan-2-ylcarbamate (6.65 g, 94%) as a white solid. An esterification test was performed to assure quantitative acid fluoride formation by dissolving Fmoc-Ile-F (5 mg) in anhydrous MeOH (0.3 mL) and DIEA (0.030 mL) and allowing to react at room temperature for 15 min. The mixture was then evaporated in vacuo and analyzed by LCMS, showed less than 1% of Fmoc-Ile-OH present.
Workup
- washwashed with ice-cold water (2×200 mL)
- dry with materialthe organic layer was dried over MgSO4
- filtrationfiltered
- customevaporated in vacuo
Sources & evidence
- ORD record
- ord-23e89ede147f47788632bdb01ae88ce8
- Source dataset
- uspto-grants-2016_08
- Patent number
- US09427479B2
Reaction notes
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