Ethyl Acetate → HCID 59166770, compound

HRID 1442958Notes

Reaction equation

HRID 1442958 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@H:8]([OH:10])[CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4].[H-].[Na+].[Cl:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Br)=[CH:23][CH:22]=1.C(OCC)(=O)C>CN(C)C=O.C(Cl)Cl>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@H:8]([O:10][CH2:25][C:24]2[CH:27]=[CH:28][C:21]([Cl:20])=[CH:22][CH:23]=2)[CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 10752873N-Boc-cis-4-hydroxy-L-proline methyl ester

Product 1

HCID 59166770HCID 59166770, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

(2S,4S)-4-Hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyester (CAS Reg. No. 227935-38-8)(300 mg, 1.0 mmol) and 60% sodium hydride mineral oil dispersion (61 mg, 1.1 mmol) were dissolved in anhydrous dimethylformamide (9 ml) at 0° C. under a nitrogen atmosphere. After 10 mins stirring 4-chlorobenzylbromide (265 mg, 1.2 mmol) in CH2Cl2 (1 ml) was added drop wise and the reaction mixture stirred to room temperature for 1 hour. The solvent was removed under reduced pressure and the residue dissolved in ethyl acetate (25 ml), washed with water (2×25 ml), dried (magnesium sulphate), filtered and evaporated under reduced pressure. The residue was purified using flash chromatography eluting with a solvent gradient 4:1 heptane:ethyl acetate, yielding the title compound (170 mg, 40% yield) as an oil.

Workup

  1. additionwas added drop wise
  2. customThe solvent was removed under reduced pressure
  3. dissolutionthe residue dissolved in ethyl acetate (25 ml)
  4. washwashed with water (2×25 ml)
  5. dry with materialdried (magnesium sulphate)
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe residue was purified
  9. washeluting with a solvent gradient 4:1 heptane

Sources & evidence

ORD record
ord-d4cbb774beee40abbb667aa28dfcc396
Source dataset
uspto-grants-2010_02
Patent number
US07659305B2

Reaction notes

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