Benzyl chloroformate → Z-L-2-Nal-OH

HRID 1757757Notes

Reaction equation

HRID 1757757 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][C@@H:12]([C:14]([OH:16])=[O:15])[NH2:13].[OH-].[Na+].Cl[C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21]>O>[CH2:23]([O:22][C:20]([NH:13][C@H:12]([C:14]([OH:16])=[O:15])[CH2:11][C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:1]=1)=[O:21])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 14798Sodium Hydroxide2×HCID 1859152-Naphthylalanine

Product 1

HCID 7023496Z-L-2-Nal-OH

Reagents, catalysts & solvents 1

HCID 962WaterSolvent3×

Procedure

5 g of 3-(2-naphthyl)-L-alanine and 0.93 g of sodium hydroxide in 12 mlof water were cooled to 0° C. and stirred while a solution of 1.4 g of sodium hydroxide in 9 ml of water and 5 ml of benzyl chloroformate wereadded simultaneously during 10 minutes. Stirring was continued for 2 hours and the mixture was allowed to come to room temperature. The mixture was diluted with water and then extracted with diethyl ether. The aqueous layer was acidified with 4 ml of concentrated hydrochloric acid and extracted with ethyl acetate. The ethyl acetate extracts were back-washed with water. The combined ethyl acetate extracts were dried over sodium sulphate, filtered, evaporated and triturated with petroleum ether (boiling point 40°-60° C.) to give 7.5 g of N-(benzyloxycarbonyl)-3-(2-naphthyl)-L-alanine of melting point 109°-111° C. (ii) A solution of 7.5 g of N-(benzyloxycarbonyl)-3-(2-naphthyl)-L-alanine in 20 ml of dry tetrahydrofuran was stirred at -8° C. and treated with 3.5 ml of N-ethylmorpholine followed by 4 ml of isobutyl chloroformate, added dropwise over a period of 10 minutes. The mixture was stirred at -8° C. for a further 20 minutes and cold (0° C.) anhydrous diethyl ether was added. The resulting white precipitate was filtered off and the cold filtrate was added dropwise to 100 ml of a stirred, cold (-8° C.) solution of diazomethane in diethyl ether. The cooling wasremoved and the solution was stirred for 3 hours. Water was added while stirring. The organic phase was washed in sequence with water, sodium bicarbonate solution and saturated sodium chloride solution and then driedover sodium sulphate. The solvent was removed by evaporation to give a yellow oil which, on evaporation with petroleum ether (boiling point 40°-60° C.), gave 9.4 g of a solid. Trituration of this solid with diethyl ether and refrigeration at 4° C. overnight gave 3.2 g of benzyl [3-diazo-1(S)-[(2-naphthyl)methyl]-2-oxopropyl]carbamate.

Workup

  1. waitwas continued for 2 hours
  2. customto come to room temperature
  3. extractionextracted with diethyl ether
  4. extractionextracted with ethyl acetate
  5. washThe ethyl acetate extracts were back-washed with water
  6. dry with materialThe combined ethyl acetate extracts were dried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customtriturated with petroleum ether (boiling point 40°-60° C.)

Sources & evidence

ORD record
ord-35c7ac068790434bb9d465219d4961a6
Source dataset
uspto-grants-1995_08
Patent number
US05446161

Reaction notes

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