Sodium hydride → (2S,4R)-N-Boc-4-(4-Bromobenzyloxy)-2-methyl-proline

HRID 49979

Reaction equation

HRID 49979 reaction equation
[H-].[Na+].C[O:4][C:5](=[O:20])[C@:6]1([CH3:19])[CH2:10][C@@H:9]([OH:11])[CH2:8][N:7]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].[Br:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26]Br)=[CH:24][CH:23]=1>C1COCC1.O>[C:12]([N:7]1[CH2:8][C@H:9]([O:11][CH2:26][C:25]2[CH:28]=[CH:29][C:22]([Br:21])=[CH:23][CH:24]=2)[CH2:10][C@@:6]1([CH3:19])[C:5]([OH:4])=[O:20])([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 685274-Bromobenzyl bromideHCID 106350101-(tert-Butyl) 2-methyl (2S,4R)-4-hydroxy-2-methylpyrrolidine-1,2-dicarboxylate

Product 1

HCID 21301005(2S,4R)-N-Boc-4-(4-Bromobenzyloxy)-2-methyl-prolineYield 28.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of sodium hydride (60% in oil) (0.12 g) (1.5 eq.) in 5 mL of dry THF was added (2S,4R)-N-Boc-4-hydroxy-2-methyl-proline methyl ester (0.55 g) in 5 mL of dry THF. The reaction mixture was stirred for 45 min., and a solution of 4-bromobenzyl bromide (0.75 g) (1.5 eq.) in 5 mL of dry THF was added. The reaction mixture was refluxed for 3 h. After cooling to RT, the reaction mixture was diluted with water and extracted with EtOAc. The aqueous layer was acidified and extracted with DCM. The combined organic extracts were washed with water, dried over MgSO4 and evaporated under reduced pressure to afford (2S,4R)-N-Boc-4-(4-bromo-benzyloxy)-2-methyl-proline (0.25 g).

Workup

  1. temperatureThe reaction mixture was refluxed for 3 h
  2. extractionextracted with EtOAc
  3. extractionextracted with DCM
  4. washThe combined organic extracts were washed with water
  5. dry with materialdried over MgSO4
  6. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-2d29d28f58b24fcfa52d6529402a7cce
Source dataset
uspto-grants-2004_03
Patent number
US06710064B2

Linked notes

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