Acetylcysteamine → [2-(Acetylamino)ethyl]-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, (4-nitrophenyl)methyl ester

HRID 482837

Reaction equation

HRID 482837 reaction equation
C(NCCS[C:8]1[CH2:14][C@H:13]2[N:10]([C:11](=[O:17])[C@H:12]2[CH2:15][CH3:16])[C:9]=1[C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][CH:23]=1)=[O:19])(=O)C.N12CCC1CC=C2.C(N(C(C)C)CC)(C)C.[C:47]([NH:50][CH2:51][CH2:52]S)(=[O:49])[CH3:48]>C(#N)C>[C:47]([NH:50][CH2:51][CH2:52][C:8]1[CH2:14][CH:13]2[N:10]([C:11](=[O:17])[CH:12]2[CH2:15][CH3:16])[C:9]=1[C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][CH:23]=1)=[O:19])(=[O:49])[CH3:48]

Participants

6

Reactant 4

HCID 14484AcetylcysteamineHCID 81531Diisopropylethylamine2×HCID 189880901-Azabicyclo[3.2.0]hept-2-eneHCID 86740674trans (+/-)-3-[[2-(Acetylamino)ethyl)thio]-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, (4-nitrophenyl)methyl ester

Product 1

HCID 86740673[2-(Acetylamino)ethyl]-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, (4-nitrophenyl)methyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Preparation of trans (±)-3-[[2-(acetylamino)ethyl)thio]-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, (4-nitrophenyl)methyl ester (XVII, R=CH3CH2 --, R'"=CH3CONH--CH2 --CH2 --, R4 = ##STR19## A solution of the bicyclic keto ester obtained in step (c) above (XV R=CH3CH2 --) (2.49 g) in acetonitrile (15 ml) is cooled to 0° C. and diisopropylethylamine (1.42 ml) is added. Then chlorodiphenylphosphate (1.72 ml) is added drop by drop keeping the temperature at 0°/-2° C. Stirring is continued for 15 minutes at 0° C., after which thin layer chromatography confirms the complete transformation of the bicyclic keto ester XV into the enol phosphate derivative XVI (R=CH3CH2 --). An additional portion of diisopropylethylamine (1.55 ml) is added followed by the slow addition of N-acetylcysteamine (1.07 g) dissolved in acetonitrile (5 ml). The reaction mixture is then stirred at 0° C. for 30 minutes and the solid which precipitates is filtered, washed with cold acetonitrile (10 ml) and diethyl ether (20 ml), and dried in vacuo at room temperature yielding 2.03 g of trans (±)-3-[[2 -(acetylamino)ethyl]-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, (4-nitrophenyl)methyl ester which melts at 174°-76° C. Additional 0.46 g of equally pure product is obtained on cooling the filtrate to -20° C. for 2 hours.

Workup

  1. customat 0°
  2. custom-2° C
  3. stirringThe reaction mixture is then stirred at 0° C. for 30 minutes
  4. customthe solid which precipitates
  5. filtrationis filtered
  6. washwashed with cold acetonitrile (10 ml) and diethyl ether (20 ml)
  7. customdried in vacuo at room temperature

Sources & evidence

ORD record
ord-c78191d3e6ca47d0933b90a74af56581
Source dataset
uspto-grants-1986_03
Patent number
US04576746

Linked notes

Loading…