Hydrochloric Acid → 4-[Benzyl(tert-butoxycarbonyl)amino]butanoic acid

HRID 985644Notes

Reaction equation

HRID 985644 reaction equation
[C:1]([O:5][C:6](=[O:20])[N:7]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:8][CH2:9][CH2:10][CH2:11][OH:12])([CH3:4])([CH3:3])[CH3:2].[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=[O:22].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.O.Cl>CN(C)C=O>[CH2:13]([N:7]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:20])[CH2:8][CH2:9][CH2:10][C:11]([OH:22])=[O:12])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 2724130Cornforth reagentHCID 22006367tert-Butyl benzyl(4-hydroxybutyl)carbamate

Product 1

HCID 225076004-[Benzyl(tert-butoxycarbonyl)amino]butanoic acidYield 40.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of benzyl-(4-hydroxy-butyl)-carbamic acid tert butyl ester (9.4 g, 33.7 mmol) in anhydrous dimethyl formamide “DMF” (40 mL) was cooled in an ice bath. Pyridinium dichromate (44 g, 117 mmol) was added in 4 portions of with 15 min intervals. The reaction mixture was allowed to stir overnight at room temperature resulting in a viscous black slurry. The slurry was poured into water (400 mL), acidified to pH 1 with concentrated HCl and extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with, 5% NaHSO4 (100 mL), water (4×300 mL). Subsequently, the organic layer was extracted with 1M NaOH (150, 75, and 50 mL). The combined aqueous layers were cooled with an ice bath and the pH was adjusted to 3 with concentrated HCl. The resulting white suspension was extracted three times with ethyl acetate (3×200 mL) and the combined organic layers were dried over Na2SO4, filtered, and the solvent was evaporated in vacuo to give N-benzyl-N-(t-butoxy-carbonyl)-4-amino-1-butanoic acid (4.0 g, 40%) as viscous oil. 1H NMR (CDCl3): δ 7.23-7.35 (m, 5H); 4.41 (bs, 2H); 3.29 (bs, 1H); 3.19 (bs, 1H); 2.33 (bs, 2H); 1.82 (bs, 2H); 1.46 (bs, 9H).

Workup

  1. customresulting in a viscous black slurry
  2. extractionextracted with ethyl acetate (3×100 mL)
  3. washThe combined organic layers were washed with, 5% NaHSO4 (100 mL), water (4×300 mL)
  4. extractionSubsequently, the organic layer was extracted with 1M NaOH (150, 75, and 50 mL)
  5. temperatureThe combined aqueous layers were cooled with an ice bath
  6. extractionThe resulting white suspension was extracted three times with ethyl acetate (3×200 mL)
  7. dry with materialthe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. customthe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-5de90c5ddf5447bea5dfc7bbc2b24df4
Source dataset
uspto-grants-2005_03
Patent number
US06872827B2

Reaction notes

Loading…