Water → 2-(4-Methoxycarbonyl-2-oxo-butylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 277204Notes

Reaction equation

HRID 277204 reaction equation
O=C1CCC(=O)N1OC(N1CCCC1C([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=O)=O.Cl.[CH3:24][O:25][C:26](=[O:33])[CH2:27][CH2:28][C:29](=[O:32])[CH2:30][NH2:31].[CH2:34]([N:36]([CH2:39][CH3:40])[CH2:37][CH3:38])C.[OH2:41].CN([CH:45]=[O:46])C>>[C:19]([O:18][C:34]([N:36]1[CH2:39][CH2:40][CH2:38][CH:37]1[C:45](=[O:46])[NH:31][CH2:30][C:29](=[O:32])[CH2:28][CH2:27][C:26]([O:25][CH3:24])=[O:33])=[O:41])([CH3:22])([CH3:21])[CH3:20]

Participants

6

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 8471TriethylamineHCID 157921Methyl Aminolevulinate HydrochlorideHCID 86757517Pyrrolidine-1,2-dicarboxylic acid 2-tert-butyl ester 1-(2,5-dioxo-pyrrolidin-1-yl) ester

Product 1

HCID 536696842-(4-Methoxycarbonyl-2-oxo-butylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 50%

Procedure

Pyrrolidine-1,2-dicarboxylic acid 2-tert-butyl ester 1-(2,5-dioxo-pyrrolidin-1-yl) ester (1.03 g, 3.3 mmol) was dissolved in DMF (30 mL) and 5-amino-4-oxo-pentanoic acid methyl ester hydrochloride salt (0.60 g, 3.3 mmol) was added. The reaction mixture was stirred at room temperature for 1 h. Triethylamine was added and stirring continued overnight (ca. 16 h). The reaction was poured into water (300 mL) and extracted with ethyl acetate (3×70 mL). The combined organic portion was extracted with saturated aqueous sodium bicarbonate (60 mL), water (2×30 mL), and brine (50 mL). The organic portion was dried over magnesium sulfate and the solvent removed in vacuo. The resulting yellow oil was chromatographed on a Biotage 40S column with ethyl acetate: hexanes (4:1) to give the title compound (0.57 g, 50%). 1HNMR (400 MHz, CDCl3): δ4.2 (m, 3H), 3.65 (s, 3H), 3.43 (m, 1.5H), 3.35 (m, 0.5H), 2.70 (m, 2H), 2.62 (m, 2H), 2.25 (bs, 0.25H), 2.15 (bs, 0.75H), 1.88 (m, 2H), 1.70 (bs, 1H), 1.25 (bs, 9H). MS: Calc'd for C11H18N2O4 (M-BOC): 242.13. Found (M-BOC+1): 243.0.

Workup

  1. stirringstirring continued overnight (ca. 16 h)
  2. extractionextracted with ethyl acetate (3×70 mL)
  3. extractionThe combined organic portion was extracted with saturated aqueous sodium bicarbonate (60 mL), water (2×30 mL), and brine (50 mL)
  4. dry with materialThe organic portion was dried over magnesium sulfate
  5. customthe solvent removed in vacuo
  6. customThe resulting yellow oil was chromatographed on a Biotage 40S column with ethyl acetate: hexanes (4:1)

Sources & evidence

ORD record
ord-2caa6345d2c7439ca4b2c619bcf8993c
Source dataset
uspto-grants-2002_03
Patent number
US06355662B1

Reaction notes

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