Pyrrolidine → Tert-butyl (2S,3R)-3-methoxy-1-oxo-1-(pyrrolidin-1-yl)butan-2-ylcarbamate

HRID 1808778Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:13]([O:15][CH3:16])[CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC[N:19]([CH:23]([CH3:25])C)[CH:20]([CH3:22])C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.N1CCCC1>C(Cl)Cl>[CH3:16][O:15][C@H:13]([CH3:14])[C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C:10](=[O:12])[N:19]1[CH2:20][CH2:22][CH2:25][CH2:23]1

Participants

Conditions

Temperature: 0 °C

Procedure

(2S,3R)-2-(Tert-butoxycarbonylamino)-3-methoxybutanoic acid (643 mg, 2.76 mmol), which is commercially available, and DIPEA (1.440 mL, 8.27 mmol) was mixed in DCM (10 mL). The mixture was cooled to 0° C. TBTU (974 mg, 3.03 mmol) was added and the mixture stirred at rt for 10 min. Pyrrolidine (0.274 mL, 3.31 mmol) was added and the resultant mixture was stirred at rt for 16 h. The mixture was diluted with DCM (10 mL). The organic phase was washed with NaHCO3 (8% in aq. solution) and brine, filtered through a phase separator and concentrated under reduced pressure. The residue was purified via Biotage (gradient; DCM/iso-propanol, 99:1 to 95:5, KP-SIL 340 g column). The solvent was removed under reduced pressure to give the title compound (0.704 g, 95%). 1H NMR (400 MHz, CD3OD) δ 1.15, 1.44, 1.82-2.05, 3.33, 3.35-3.52, 3.54-3.65, 3.66-3.79, 4.36. Total no of protons: 25. LCMS (M+H)+: 287.

Workup

washThe organic phase was washed with NaHCO3 (8% in aq. solution) and brine
filtrationfiltered through a phase separator
concentrationconcentrated under reduced pressure
customThe residue was purified via Biotage (gradient; DCM/iso-propanol, 99:1 to 95:5, KP-SIL 340 g column)
customThe solvent was removed under reduced pressure

Sources & evidence

ORD record: ord-be2d75e01eab4d32a877bc1d8068468d
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08361998B2

Reaction notes

Loading…