N-bromobutanimide → (3R,8aR)-3-Bromomethyl-3-methyltetrahydropyrrolo[2,1-c][1,4]oxazine-1,4-dione
Reaction equation
C1C(=O)N([Br:8])C(=O)C1.[CH3:9][C:10](=[CH2:21])[C:11]([N:13]1[CH2:17][CH2:16][CH2:15][C@@H:14]1[C:18]([OH:20])=[O:19])=[O:12]>CN(C=O)C>[Br:8][CH2:21][C@:10]1([CH3:9])[O:19][C:18](=[O:20])[C@H:14]2[CH2:15][CH2:16][CH2:17][N:13]2[C:11]1=[O:12]Participants
Procedure
NBS (16 g, 89.9 mmol) was dissolved in DMF (50 ml) and added at room temperature to a solution of (2R)-1-(2-methylacryloyl)pyrrolidine-2-carboxylic acid (11.5 g, contains 8.0 g of the corresponding starting material, 43.4 mmol) in DMF (50 ml). The mixture was stirred for 20 h and evaporated at 80-90° C. The residue was mixed with water (250 ml) and extracted with ethyl acetate (4×80 ml). The combined ethyl acetate phases were washed with 1 M NaHCO3 solution (2×50 ml) and water (1×50 ml). The organic phase was dried over Na2SO4 and evaporated. The yield of the crude oil was 9.3 g. Ethyl acetate (10 ml) was added and the mixture was stirred in an ice bath. The precipitated product was filtered and washed with cooled ethyl acetate. The yield was 1.2 g. 1H NMR (DMSO-d6): 1.58 (3H, s), 1.75-2.10 (3H, m), 2.25 (1H, m), 3.30-3.55 (2H, m), 3.87 (1H, d, J=11.4 Hz), 4.03 (1H, d, J=11.4 Hz), 4.70 (1H, m).
Workup
- customevaporated at 80-90° C
- additionThe residue was mixed with water (250 ml)
- extractionextracted with ethyl acetate (4×80 ml)
- washThe combined ethyl acetate phases were washed with 1 M NaHCO3 solution (2×50 ml) and water (1×50 ml)
- dry with materialThe organic phase was dried over Na2SO4
- customevaporated
- additionEthyl acetate (10 ml) was added
- stirringthe mixture was stirred in an ice bath
- filtrationThe precipitated product was filtered
- washwashed with cooled ethyl acetate
Sources & evidence
- ORD record
- ord-a3a42a8401b34b999aa18c3e4a81b737
- Source dataset
- uspto-grants-2008_06
- Patent number
- US07390923B2
Reaction notes
Loading…