Methanol → Boc-(R)-alpha-(4-bromobenzyl)proline

HRID 2182615Notes

Reaction equation

HRID 2182615 reaction equation
C([O:3][C:4](=[O:25])[C@:5]1([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][CH:19]=2)[CH2:9][CH2:8][CH2:7][N:6]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])C.[Li+].[OH-].C1COCC1.CO>O>[C:13]([O:12][C:10]([N:6]1[CH2:7][CH2:8][CH2:9][C@@:5]1([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][CH:19]=1)[C:4]([OH:25])=[O:3])=[O:11])([CH3:16])([CH3:14])[CH3:15]

Participants

6

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 69212228N-(tert-butoxycarbonyl)-2-(4-bromobenzyl)proline ethyl ester

Product 1

HCID 2761850Boc-(R)-alpha-(4-bromobenzyl)prolineYield 108%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of N-(tert-butoxycarbonyl)-2-(4-bromobenzyl)proline ethyl ester (3.00 g), LiOH (10 mmol), THF (25 mL), MeOH (10 mL) and H2O (5 mL) was stirred at room temperature overnight. The mixture was then heated at 74° C. overnight. The mixture was concentrated in vacuo, and water was added. The mixture was washed with Et2O and the aqueous layer was made acidic with the addition of 1N H2SO4. The aqueous layer was extracted with EtOAc. The EtOAc layer was washed with brine, dried over Na2SO4, and evaporated to give N-(tert-butoxycarbonyl)-2-(4-bromobenzyl)proline (3.02 g). MS (m/z) 284 (MH+-t-Boc); mp: 143.9° C.

Workup

  1. temperatureThe mixture was then heated at 74° C. overnight
  2. concentrationThe mixture was concentrated in vacuo, and water
  3. additionwas added
  4. washThe mixture was washed with Et2O
  5. additionthe aqueous layer was made acidic with the addition of 1N H2SO4
  6. extractionThe aqueous layer was extracted with EtOAc
  7. washThe EtOAc layer was washed with brine
  8. dry with materialdried over Na2SO4
  9. customevaporated

Sources & evidence

ORD record
ord-76ba3c8e568549a2809cf05b71b54723
Source dataset
uspto-grants-2005_05
Patent number
US06897225B1

Reaction notes

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