Ethyl alpha-oxobenzenebutanoate → Ammonium Hydroxide

HRID 2417773Notes

Reaction equation

HRID 2417773 reaction equation
Br.[NH2:2][C@H:3]([C:5]([N:7]1[C@H:15]([C:16]([OH:18])=[O:17])[CH2:14][C:9]2([S:13][CH2:12][CH2:11][S:10]2)[CH2:8]1)=[O:6])[CH3:4].O=[C:20]([CH2:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:21]([O:23][CH2:24][CH3:25])=[O:22]>CO>[OH-:6].[NH4+:2].[C:21]([CH:20]([NH:2][C@H:3]([C:5]([N:7]1[C@H:15]([C:16]([OH:18])=[O:17])[CH2:14][C:9]2([S:13][CH2:12][CH2:11][S:10]2)[CH2:8]1)=[O:6])[CH3:4])[CH2:26][CH2:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)([O:23][CH2:24][CH3:25])=[O:22]

Participants

5

Reactant 2

HCID 562087Ethyl alpha-oxobenzenebutanoateHCID 13373617HCID 13373617, compound

Product 2

HCID 14923Ammonium HydroxideYield 7%HCID 13373618HCID 13373618, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Dissolve the 7-[(S)-alanyl]-1,4-dithia-7-azaspiro[4.4]nonane-8(S)-carboxylic acid hydrobromide (prepared in paragraph E next above) in 100 ml of absolute methanol. Add 0.5 g of 2-oxo-4-phenylbutyric acid, ethyl ester and 10 ml of 3A molecular sieve pellets and stir the mixture at room temperature for eighteen hours. Filter the reaction mixture and treat the filtrate with 0.30 g of sodium cyanoborohydride at room temperature for two hours. Concentrate the mixture under nitrogen and dilute the oil with 5% hydrochloric acid to pH 2 to 4 and stir at room temperature for one hour. Adjust the pH of the solution to pH 8 with 2.5 N sodium hydroxide solution and absorb the solution in 150 ml of XAD-2 resin. Elute the resin with 800 ml of water and then with 800 ml of methanol. Concentrate the methanol solution, place the residue on a column of silca gel (100 g, 60-200 mesh) and elute with chloroform:isopropanol:7% ammonium hydroxide 1:1:1 (organic layer) to obtain 7-[N-(1-carboethoxy-3-phenylpropyl)-(S)-alanyl]-1,4-dithia-7-azaspiro[4.4]nonane-8(S)-carboxylic acid, a white solid, m.p. 56°-60° C., [α]D26 -25.5° (ethanol).

Workup

  1. filtrationFilter the reaction mixture
  2. additiontreat the filtrate with 0.30 g of sodium cyanoborohydride at room temperature for two hours
  3. concentrationConcentrate the mixture under nitrogen
  4. additiondilute the oil with 5% hydrochloric acid to pH 2 to 4
  5. stirringstir at room temperature for one hour
  6. customabsorb the solution in 150 ml of XAD-2 resin
  7. washElute the resin with 800 ml of water
  8. concentrationConcentrate the methanol solution, place the residue on a column of silca gel (100 g, 60-200 mesh)
  9. washelute with chloroform

Sources & evidence

ORD record
ord-a817ee57730642c486266db20d93fff7
Source dataset
uspto-grants-1984_09
Patent number
US04470972

Reaction notes

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