Ethyl Acetate → (E)-(7S,10S,13S)-13-tert-Butoxycarbonylamino-10-isopropyl-9,12-dioxo-2-oxa-8,11-diazabicyclo[13.2.2]nonadeca-1(18),4,15(19),16-tetraene-7-carboxylic acid methyl ester

HRID 2371324

Reaction equation

HRID 2371324 reaction equation
[CH3:1][O:2][C:3](=[O:38])[C@@H:4]([NH:8][C:9](=[O:37])[C@@H:10]([NH:14][C:15](=[O:36])[C@@H:16]([NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25]C=C)=[CH:20][CH:19]=1)[CH:11]([CH3:13])[CH3:12])[CH2:5][CH:6]=[CH2:7].CCOC(C)=O>ClC(Cl)CCl>[CH3:1][O:2][C:3]([C@H:4]1[NH:8][C:9](=[O:37])[C@H:10]([CH:11]([CH3:13])[CH3:12])[NH:14][C:15](=[O:36])[C@@H:16]([NH:28][C:29]([O:31][C:32]([CH3:34])([CH3:35])[CH3:33])=[O:30])[CH2:17][C:18]2=[CH:23][CH:22]=[C:21]([CH:20]=[CH:19]2)[O:24][CH2:25][CH:7]=[CH:6][CH2:5]1)=[O:38]

Participants

4

Reactant 2

HCID 8857Ethyl AcetateHCID 66847339(S)-2-{(S)-2-[(S)-3-(4-Allyloxy-phenyl)-2-tert-butoxycarbonylamino propionylamino]-3-methylbutyrylamino}-pent-4-enoic acid methyl ester

Product 1

HCID 66847119(E)-(7S,10S,13S)-13-tert-Butoxycarbonylamino-10-isopropyl-9,12-dioxo-2-oxa-8,11-diazabicyclo[13.2.2]nonadeca-1(18),4,15(19),16-tetraene-7-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 65741,1,2-TrichloroethaneSolvent

Procedure

Diene 44 (1.80 g, 3.39 mmol) was dissolved in anhydrous 1,1,2-trichloroethane (0.01M) under an atmosphere of argon. GSGC (0.10 equiv) was added. The mixture was heated at reflux for one hour. Two further additions of GSGC (0.10 equiv) were added and after each the reaction mixture was subjected to one h and eighteen h of reflux respectively. This was then cooled and concentrated in vacuo. The crude material was purified by flash chromatography on silica using a gradient of EtOAc and (50/70) petroleum ether to yield a brown solid, 0.205 g, 12%. Rf=0.24 (1/1 EtOAc/(50/70) petroleum ether). m.p. 105-107° C.

Workup

  1. additionGSGC (0.10 equiv) was added
  2. temperatureThe mixture was heated
  3. temperatureat reflux for one hour
  4. additionTwo further additions of GSGC (0.10 equiv) were added
  5. temperatureof reflux respectively
  6. temperatureThis was then cooled
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by flash chromatography on silica using a gradient of EtOAc and (50/70) petroleum ether
  9. customto yield a brown solid, 0.205 g, 12%

Sources & evidence

ORD record
ord-0f0e2fb597524808b586a83d932a8bd0
Source dataset
uspto-grants-2014_04
Patent number
US08710178B2

Linked notes

Loading…