Benzyl chloroformate → 2-{[(Benzyloxy)carbonyl]amino}-3-(thiophen-2-yl)propanoic acid

HRID 650210Notes

Reaction equation

HRID 650210 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][CH:7]([C:9]([OH:11])=[O:10])[NH2:8].C([O-])([O-])=O.[K+].[K+].[C:18](Cl)([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19].CCOC(C)=O.CC(O)=O.CC#N.O>O>[CH2:21]([O:20][C:18]([NH:8][CH:7]([C:9]([OH:11])=[O:10])[CH2:6][C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)=[O:19])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 10387Benzyl chloroformateHCID 11430Potassium CarbonateHCID 914442-ThienylalanineHCID 131719237EtOAc AcOH CH3CN H2O

Product 1

HCID 128068302-{[(Benzyloxy)carbonyl]amino}-3-(thiophen-2-yl)propanoic acidYield 98%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Into a 500 ml flask was placed 3.0 g of 3-(2-Thienyl)-D,L-alanine (optically active material in the L-form is available from Aldrich or SIGMA and could be used t obtain an optically active product) in 75 ml H2O/60 ml dioxane, and 5.6 g K2CO3 was added, followed by 2.85 ml of carbobenzyloxy chloride. The mixture was stirred rapidly for 1 hour. TLC (21/7/7/9, EtOAc/AcOH/CH3CN/H2O; showed that the starting material was gone. A new higher Rf product was seen. The dioxane was concentrated off and the aqueous layer was washed with Et2O (75 ml). The aqueous layer was mixed with CH2Cl2 (150 ml) and acidified to pH=2.0 with 5N HCl. The desired N-(Benzyloxycarbonyl)-3-(2-thienyl)-D,L-alanine was extracted with CH2Cl2. The organic layer was separated and dried with Na2SO4, filtered, and concentrated to give 5.05 g of desired N-(Benzyloxycarbonyl)-3-(2-thienyl)-D,L-alanine (98% yield).

Workup

  1. customInto a 500 ml flask was placed
  2. concentrationThe dioxane was concentrated off
  3. washthe aqueous layer was washed with Et2O (75 ml)
  4. additionThe aqueous layer was mixed with CH2Cl2 (150 ml)
  5. extractionThe desired N-(Benzyloxycarbonyl)-3-(2-thienyl)-D,L-alanine was extracted with CH2Cl2
  6. customThe organic layer was separated
  7. dry with materialdried with Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-2cc0dda7311d414f888b3813edc29826
Source dataset
uspto-grants-2001_08
Patent number
US06271235B1

Reaction notes

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