Sodium Carbonate → HCID 20438169, compound

HRID 1979679Notes

Reaction equation

HRID 1979679 reaction equation
[NH2:1][N:2]1[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.Br[CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[C:13]([O:12][C:10](=[O:11])[CH2:9][NH:1][N:2]1[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1)([CH3:16])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 20315N-AminomorpholineHCID 79177tert-Butyl bromoacetate

Product 1

HCID 20438169HCID 20438169, compoundYield 29.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of N-aminomorpholine (4 g), t-butyl bromoacetate (7.6 g) and sodium carbonate (2.1 g) in 20 ml of DMF was stirred at room temperature overnight. After concentration in vacuo, the residue was taken up in ethyl acetate. The organic solution was washed with water, dried, filtered and concentrated in vacuo to give 2.5 g of crude N-(morpholino)glycine t-butyl ester (compound III-A). This crude compound was used without further purification. To a solution of 5 g of the product (I-D) in 10 ml of methylene chloride was added a solution of 2.5 g of compound (III-A) and 5 ml of pyridine in 5 ml of methylene chloride over a period of 10 minutes. After 16 hours the reaction mixture was washed successively with 1N hydrochloric acid, saturated aqueous sodium bicarbonate, and once with brine. The organic solution was dried, filtered, concentrated in vacuo, and purified by dry column chromatography to give 3.5 g of oily product (III-B), N-(morpholino)-N-[N-[(1S)-1-ethoxycarbonyl-3-phenylpropyl]-N-(2,2,2-trichloroethoxycarbonyl)-L-alanyl]glycine t-butyl ester: ##STR21## To a solution of 0.6 g of product (III-B) in 10 ml of glacial acetic acid was added 2 g of zinc dust. After three hours the mixture was filtered through celite and concentrated in vacuo. The residue was taken up in ethyl acetate and washed with water. The organic solution was dried, filtered, concentrated in vacuo, and chromatographed to give 0.4 g of product (III-C), N-(morpholine)-N-[N-[(1S)-1-ethoxycarbonyl-3-phenylpropyl]L-alanyl]glycine t-butyl ester: ##STR22## The dihydrochloric acid salt of the free acid was formed by bubbling dry hydrogen chloride gas into an ethereal solution containing 0.5 g of product (III-C) at 0° C. for 2.5 hours. Concentration in vacuo gave 0.4 g of solid product.

Workup

  1. concentrationAfter concentration in vacuo
  2. washThe organic solution was washed with water
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fb141d7af83f4131be2e97d630004c46
Source dataset
uspto-grants-1984_11
Patent number
US04482544

Reaction notes

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