Triethylamine → 1-O-tert-butyl 2-O-methyl (2S)-5-oxopyrrolidine-1,2-dicarboxylate

HRID 1099004Notes

Reaction equation

HRID 1099004 reaction equation
[O:1]=[C:2]1[NH:6][C@H:5]([C:7]([O:9][CH3:10])=[O:8])[CH2:4][CH2:3]1.C(N(CC)CC)C.[O:18](C(OC(C)(C)C)=O)[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[O:1]=[C:2]1[N:6]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:18])[C@H:5]([C:7]([O:9][CH3:10])=[O:8])[CH2:4][CH2:3]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 78646Methyl 5-oxo-L-prolinateHCID 90495Di-tert-butyl dicarbonate

Product 1

HCID 108684851-O-tert-butyl 2-O-methyl (2S)-5-oxopyrrolidine-1,2-dicarboxylateYield 96%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of commercially available methyl 5-oxo-L-prolinate (20 g, 140 mmol) in DCM (200 ml) were added triethylamine (19.6 ml, 140 mmol), DMAP (17.2 g, 140 mmol) and then dropwise a solution of BOC2O (61 g, 280 mmol) in DCM (100 ml). The resulting red mixture was stirred at room temperature for 2 hours. Then the solvent was removed under reduced pressure and the crude material was purified by chromatography on silica gel eluting with cyclohexane/ethyl acetate (7:3 to 4:6) to afford (after a trituration in hexane/diethylether 1:1) the title compound as a white solid (32.4 g, 96%); Rf (cyclohexanes:ethyl acetate=65:35): 0.21; 1H NMR (300 MHz, CDCl3) δ(ppm): 4.62 (dd, 1H), 3.78 (s, 3H), 2.68-2.58 (m, 1H), 2.52-2.45 (m, 1H), 2.37-2.27 (m, 1H), 2.08-1.97 (m, 1H), 1.48 (s, 9H).

Workup

  1. customThen the solvent was removed under reduced pressure
  2. customthe crude material was purified by chromatography on silica gel eluting with cyclohexane/ethyl acetate (7:3 to 4:6)

Sources & evidence

ORD record
ord-4782d039d5ae49889ebe3a3def58ffe0
Source dataset
uspto-grants-2012_03
Patent number
US08143306B2

Reaction notes

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