p-Xylyl bromide → 4-[(tert-Butoxycarbonyl)amino]-2-(4-methylbenzyl)-butanoic acid

HRID 1192439Notes

Reaction equation

HRID 1192439 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH2:20][C:19]1=[O:23])=[O:17])([CH3:14])([CH3:13])[CH3:12].[CH3:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29]Br)=[CH:27][CH:26]=1.C1C[O:36]CC1>>[C:11]([O:15][C:16]([NH:18][CH2:22][CH2:21][CH:20]([CH2:24][C:25]1[CH:32]=[CH:31][C:28]([CH3:29])=[CH:27][CH:26]=1)[C:19]([OH:23])=[O:36])=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

5

Reactant 4

HCID 7721p-Xylyl bromideHCID 8028Tetrahydrofuran3×HCID 3790001-Pyrrolidinecarboxylic acid, 2-oxo-, 1,1-dimethylethyl esterHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 510720044-[(tert-Butoxycarbonyl)amino]-2-(4-methylbenzyl)-butanoic acidYield 49%

Conditions

Temperature
-78 °C

Procedure

To a solution containing LiHMDS (1.0M, 11.3 mL, 11 mmol) in 40 mL of THF under a nitrogen atmosphere at −78C was added a solution of 2-Oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (2.gg, 11 mmol) in 15 mL of THF dropwise over 5 minutes. After complete addition, the reaction was allowed to stir at −78° C. for 45 minutes, followed by the addition of a solution containing 4-methyl benzyl bromide (2.1 g, 11 mmol) in 15 mL of THF dropwise over 5 minutes. The reaction was allowed to stir at −78C for 1 hour then warmed to 0 C and stirred for 1 hour. The mixture was quenched with 36 mL of 3M LiOH and allowed to stir at room temperature overnight. The reaction was diluted with water and washed with ether. The aqueous phase was acidified with 1N HCl and extracted with DCM. The organic phase was dried over magnesium sulfate. Filtration and removal of solvent gave 4-tert-Butoxycarbonylamino-2-(4-methylbenzyl)-butyric acid (1.61 g, 49%.) LCMS (APCI−) m/z 306 [M-Boc-H]−; Rt: 2.14 min.

Workup

  1. additionAfter complete addition
  2. additionfollowed by the addition of a solution
  3. stirringto stir at −78C for 1 hour
  4. temperaturethen warmed to 0 C
  5. stirringstirred for 1 hour
  6. customThe mixture was quenched with 36 mL of 3M LiOH
  7. stirringto stir at room temperature overnight
  8. additionThe reaction was diluted with water
  9. washwashed with ether
  10. extractionextracted with DCM
  11. dry with materialThe organic phase was dried over magnesium sulfate
  12. filtrationFiltration and removal of solvent

Sources & evidence

ORD record
ord-76ff3535b62b4b0b8271f6ab1657362f
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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