4-Methylmorpholine → carbobenzoxy-beta-alanyl-L-proline t-butyl ester

HRID 27347

Reaction equation

HRID 27347 reaction equation
[C:1]([NH:11][CH2:12][CH2:13][C:14]([OH:16])=O)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.Cl.[C:33]([O:37][C:38](=[O:44])[C@@H:39]1[CH2:43][CH2:42][CH2:41][NH:40]1)([CH3:36])([CH3:35])[CH3:34]>C(N(CC)CC)C.CN(C)C=O.O1CCCC1>[C:33]([O:37][C:38](=[O:44])[C@@H:39]1[CH2:43][CH2:42][CH2:41][N:40]1[C:14](=[O:16])[CH2:13][CH2:12][NH:11][C:1]([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2])([CH3:36])([CH3:34])[CH3:35]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 75313N-Benzyloxycarbonyl-beta-alanineHCID 6453107tert-Butyl L-prolinate hydrochloride

Product 1

HCID 54135485carbobenzoxy-beta-alanyl-L-proline t-butyl ester

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

4.46 g. of carbobenzoxy-β-alanine is dissolved in 20 ml. of tetrahydrofuran and the resulting solution cooled to -10° C. With constant stirring of the solution, 2.4 ml. of N-methylmorpholine followed by 2.6 ml. of isobutylchloroformate are added and the resulting reaction mixture is stirred thereafter for approximately 5 minutes at -10° C. 4.16 g. of L-proline t-butyl ester hydrochloride in 20 ml. of dimethylformamide and 2.8 ml. of triethylamine is added to the reaction mixture which is thereafter stirred overnight, while slowly warming to room temperature. The solvent of the reaction mixture is evaporated in vacuo at 30°-35°. The residue is dissolved in 800 ml. of ethyl acetate which is washed with (2×150 ml.) a 10% citric acid solution, with (1×150 ml.) water, with (2×150 ml.) saturated solution of sodium bicarbonate and then with (2×100 ml.) water. The organic layer is dried with anhydrous magnesium sulfate and the solvent evaporated to yield carbobenzoxy-β-alanyl-L-proline t-butyl ester.

Workup

  1. customthe resulting reaction mixture
  2. stirringis stirred
  3. stirringis thereafter stirred overnight
  4. customThe solvent of the reaction mixture is evaporated in vacuo at 30°-35°
  5. dissolutionThe residue is dissolved in 800 ml
  6. washof ethyl acetate which is washed with (2×150 ml.) a 10% citric acid solution
  7. dry with materialThe organic layer is dried with anhydrous magnesium sulfate
  8. customthe solvent evaporated

Sources & evidence

ORD record
ord-c7cd6af73aca49feafad7a587907044d
Source dataset
uspto-grants-1980_09
Patent number
US04221706

Linked notes

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