Triethylamine → N-carbobenzoxy-L-alanyl-N-(indan-2-yl)glycine tertbutyl ester

HRID 621162Notes

Reaction equation

HRID 621162 reaction equation
[C:1]([NH:11][C@H:12]([C:14]([OH:16])=O)[CH3:13])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C(N(CC)CC)C.C(Cl)(=O)OCC.[C:30]([O:34][C:35](=[O:47])[CH2:36][NH:37][CH:38]1[CH2:46][C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH2:39]1)([CH3:33])([CH3:32])[CH3:31]>O1CCCC1.C(Cl)(Cl)Cl.O>[C:30]([O:34][C:35](=[O:47])[CH2:36][N:37]([C:14](=[O:16])[C@H:12]([CH3:13])[NH:11][C:1]([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2])[CH:38]1[CH2:39][C:40]2[C:45](=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH2:46]1)([CH3:33])([CH3:31])[CH3:32]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 736104N-carbobenzyloxyalanineHCID 13132278tert-butyl 2-[(2,3-dihydro-1H-inden-2-yl)amino]acetate

Product 1

HCID 14128700N-carbobenzoxy-L-alanyl-N-(indan-2-yl)glycine tertbutyl esterYield 86.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-Carbobenzoxy-L-alanine (21.8 g) and 12.3 ml of triethylamine are dissolved in 200 ml of tetrahydrofuran, and 8.5 of ethyl chlorocarbonate is added dropwise at -15° C. with stirring. After the dropping, stirring is continued for 15 minutes, and then a solution of 22 g of (indan-2-yl)glycine tert-butyl ester in 100 ml of chloroform is added dropwise at -10° C. or below. After stirring at room temperature for an hour, the reaction mixture is poured into 500 ml of water, and the chloroform layer is separated and the chloroform is distilled off. The residue is dissolved in 300 ml of ethyl acetate, the solution is washed with two 50-ml portions of 1N aqueous sodium hydroxide, one 50-ml portion of water, two 50-ml portions of 20% aqueous phosphoric acid and one 50-ml portion of water, in that order, and then dried over anhydrous magnesium sulfate, and the solvent is distilled off to give 35 g of N-carbobenzoxy-L-alanyl-N-(indan-2-yl)glycine tertbutyl ester as an oil. This is dissolved in 300 ml of methanol and, after addition of 7 g of oxalic acid and 3.5 g of 10% palladium-carbon (containing 50% water), is subjected to catalytic reduction at ordinary temperature and ordinary pressure. After the reaction, the catalyst is filtered off, the filtrate is distilled off under reduced pressure, and 500 ml of ethanol is added to the residue. On cooling, a precipitate forms, which is collected by filtration and dried to give 21.8 g of L-alanyl-N-(indan-2-yl)glycine tert-butyl ester oxalate melting at 138°-141° C.

Workup

  1. stirringAfter the dropping, stirring
  2. stirringAfter stirring at room temperature for an hour
  3. customthe chloroform layer is separated
  4. distillationthe chloroform is distilled off
  5. dissolutionThe residue is dissolved in 300 ml of ethyl acetate
  6. washthe solution is washed with two 50-ml portions of 1N aqueous sodium hydroxide, one 50-ml portion of water, two 50-ml portions of 20% aqueous phosphoric acid and one 50-ml portion of water, in that order
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationthe solvent is distilled off

Sources & evidence

ORD record
ord-684b4e5580d84576af55efa377c60ecf
Source dataset
uspto-grants-1989_04
Patent number
US04822818

Reaction notes

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