Methyl iodide → (2R,4R)-4-Hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

HRID 908447Notes

Reaction equation

HRID 908447 reaction equation
IC.[C:3]([O:7][C:8]([N:10]1[CH2:14][C@H:13]([OH:15])[CH2:12][C@@H:11]1[C:16]([OH:18])=[O:17])=[O:9])([CH3:6])([CH3:5])[CH3:4].[C:19](=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[OH:15][C@H:13]1[CH2:14][N:10]([C:8]([O:7][C:3]([CH3:6])([CH3:4])[CH3:5])=[O:9])[C@@H:11]([C:16]([O:18][CH3:19])=[O:17])[CH2:12]1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 688616N-Boc-cis-4-hydroxy-D-proline

Product 1

HCID 6951202(2R,4R)-4-Hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterYield 86.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

Iodomethane (4.17 ml) was added to (2R,4R)-1-tert-butoxycarbonyl-4-hydroxy-pyrrolidine-2-carboxylic acid (15.00 g) in DMF (100 ml) at 0° C. Caesium carbonate (25.4 g) was added in one portion and the resulting mixture stirred at 20° C. for 16 hours. The reaction mixture was diluted with water (150 ml) and extracted with dichloromethane (2×150 ml). The combined organics were washed with brine (100 ml), dried over Magnesium sulphate, filtered and evaporated to dryness to give O1-tert-butyl O2-methyl (2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxylate (13.83 g) as a yellow oil. 1 NMR Spectrum: (DMSOd6) 1.32 (9H, s); 1.77-1.85 (1H, m); 2.24-2.38 (1H, m); 3.07-3.15 (1H, m); 3.47 (1H, q); 3.63 (3H, t); 4.16-4.23 (2H, m); 4.92-4.98 (1H, m).

Workup

  1. extractionextracted with dichloromethane (2×150 ml)
  2. washThe combined organics were washed with brine (100 ml)
  3. dry with materialdried over Magnesium sulphate
  4. filtrationfiltered
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-e22e6227e0f042579ddb2820f3a64942
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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