Pyridine → 2-Methyl-2-propanyl (2S,4S)-2-carbamoyl-4-fluoro-1-pyrrolidinecarboxylate
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][C@@H:14]([F:16])[CH2:13][C@H:9]1[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:17]1C=CC=CC=1.C(=O)(O)[O-].[NH4+]>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:15][C@@H:14]([F:16])[CH2:13][C@H:9]1[C:10]([NH2:17])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]Participants
Conditions
- Temperature
- 20 °C
Procedure
A reactor was charged with (4S)-1-(tert-butoxycarbonyl)-4-fluoro-L-proline (130 g, 1 wt, 1 eq.), dichloromethane (520 mL, 4 vol), pyridine (55 mL, 0.4 vol, 1.2 eq), and Boc-anhydride (145 g, 1.1 wt, 1.2 eq.). The reaction solution was stirred at approximately 20° C. for 2 hours. The reactor was charged with ammonium bicarbonate (62 g, 0.5 wt, 1.44 eq), and was stirred at approximately 20° C. overnight. The reaction was filtered over a bed of celite (130 g, 1 wt), and the filter cake was washed with dichloromethane (260 mL, 2 vol). The filtrate was concentrated to a volume of 3 volumes, heptane (520 mL, 4 vol) was added, and again concentrated to a final volume of 3 volumes. Heptane (390 mL, 3 vol) was added, and the reaction was cooled to approx. 5° C. for 30 min.
Workup
- stirringwas stirred at approximately 20° C. overnight
- filtrationThe reaction was filtered over a bed of celite (130 g, 1 wt)
- washthe filter cake was washed with dichloromethane (260 mL, 2 vol)
- concentrationThe filtrate was concentrated to a volume of 3 volumes, heptane (520 mL, 4 vol)
- additionwas added
- concentrationagain concentrated to a final volume of 3 volumes
- additionHeptane (390 mL, 3 vol) was added
- temperaturethe reaction was cooled to approx. 5° C. for 30 min.
Sources & evidence
- ORD record
- ord-52c44737269e465cbba3d0370686e649
- Source dataset
- uspto-grants-2008_12
- Patent number
- US07462641B2
Reaction notes
Loading…