Ethyl alpha-oxobenzenebutanoate → Ammonium Hydroxide

HRID 2226405Notes

Reaction equation

HRID 2226405 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 3° A. 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 2.5N sodium hydroxide solution and absorbed the solution in 150 ml of a 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 silica 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. customabsorbed the solution in 150 ml of a XAD-2 resin
  7. washElute the resin with 800 ml of water
  8. concentrationConcentrate the methanol solution, place the residue on a column of silica gel (100 g, 60-200 mesh)
  9. washelute with chloroform

Sources & evidence

ORD record
ord-c28a783b3ceb472fadb639bce9c613ec
Source dataset
uspto-grants-1994_09
Patent number
US05348944

Reaction notes

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