4-Methylmorpholine → HCID 67773057, compound
Reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]([CH3:15])[CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(O[N:24]1N=NC2C=[CH:28][CH:29]=[CH:30][C:25]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH3:38]N1CCOCC1.N1CCCC1>CN(C=O)C>[CH3:14][C:13]([CH3:15])([CH3:38])[C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C:10](=[O:12])[N:24]1[CH2:25][CH2:30][CH2:29][CH2:28]1Participants
Conditions
- Temperature
- 0 °C
Procedure
(S)-2-(Tert-butoxycarbonylamino)-3-methylbutanoic acid (7.00 g, 30.3 mmol) and TBTU (9.72 g, 30.27 mmol) was mixed in DMF (70 mL). The mixture was cooled to 0° C. and NMM (3.99 mL, 36.3 mmol) was added. After 10 min was pyrrolidine (3.00 mL, 36.32 mmol) added. The resultant mixture was stirred at 0° C. for 30 min. and at rt over night. The mixture was concentrated and the residue dissolved in DCM (250 mL). The organic phase was washed with NaHCO3 (saturated, 2×200 mL) and brine (200 mL), filtered through a phase separator and concentrated under reduced pressure. The residue was purified via Biotage (gradient; DCM/iso-propanol, 99:1 to 90:10, KP-SIL 340 g column). The solvent was removed under reduced pressure to give the title compound (6.4 g, 74%). 1H NMR (400 MHz, CDCl3) δ 0.99, 1.43, 1.80-2.01, 3.31-3.45, 3.47-3.59, 3.67-3.79, 4.29, 5.28. Total no of protons: 27. LCMS (M+H)+: 285.
Workup
- concentrationThe mixture was concentrated
- dissolutionthe residue dissolved in DCM (250 mL)
- washThe organic phase was washed with NaHCO3 (saturated, 2×200 mL) and brine (200 mL)
- filtrationfiltered through a phase separator
- concentrationconcentrated under reduced pressure
- customThe residue was purified via Biotage (gradient; DCM/iso-propanol, 99:1 to 90:10, KP-SIL 340 g column)
- customThe solvent was removed under reduced pressure
Sources & evidence
- ORD record
- ord-b99e8dd0297244a18c8fabb200eea2a8
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08361998B2
Reaction notes
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