Hydrochloric Acid → HCID 86654808, compound

HRID 217902Notes

Reaction equation

HRID 217902 reaction equation
[O:1]=[C:2]1[C:11]2[N:10]=[C:9]([C:12](=[O:20])[NH:13][O:14][CH2:15][CH2:16][CH2:17][CH:18]=[CH2:19])[CH:8]=[C:7]([C:21]([O:23]C)=[O:22])[C:6]=2[C:5]2[NH:25][C:26]([C:28]([O:30]C)=[O:29])=[CH:27][C:4]=2[C:3]21OCC[O:32]2.Cl.C(Cl)Cl.CO.[Li+].[OH-]>C1COCC1>[O:32]=[C:3]1[C:2](=[O:1])[C:11]2[N:10]=[C:9]([C:12](=[O:20])[NH:13][O:14][CH2:15][CH2:16][CH2:17][CH:18]=[CH2:19])[CH:8]=[C:7]([C:21]([OH:23])=[O:22])[C:6]=2[C:5]2[NH:25][C:26]([C:28]([OH:30])=[O:29])=[CH:27][C:4]1=2

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 3939Lithium HydroxideHCID 21226129Dichloromethane methanolHCID 53247194HCID 53247194, compound

Product 1

HCID 86654808HCID 86654808, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of the product from EXAMPLE 3 (4, 32 mg, 64 μMol) in THF (6 mL) was treated with 1N HCl (0.6 mL) was kept at 45-47° C. for 24 hours. The reaction mixture was cooled to room temperature. TLC (DCM-MeOH 95:5) shows no 4 (Rf=0.75) and one major product (Rf=0.4). The solution was concentrated on a rotary evaporator to remove THF. The resulting mixture was partitioned between EtOAc (25 mL) and saturated aqueous NaCl (25 mL). The organic layer was separated and allowed to stand for 15 minutes. The organic solution was decanted from some aqueous droplets. It was then evaporated at reduced pressure to give an orange solid. The solid was dissolved in 0.25 M LiOH (1 mL, 0.25 mMol). The resulting black solution was stirred at room temperature for 24 hours. The reaction mixture was then acidified by dropwise addition of concentrated HCl (3 drops from a Pasteur pipet) to give a slurry of an orange solid. The slurry was cooled on an ice bath for 10 minutes then the solid was collected by filtration, rinsing with ice-cold water (2×2 mL) and Et2O (2×2 mL). The solid was then dried under vacuum for 6 hours to afford 5 (13.5 mg, 51%). MS (AP− taken from a MeOH solution) 444 (M+MeOH−1), 412 (m−1). NMR (DMSO-d6, δ), 13.55 (br, 1H, CO2H), 12.65 (br, 1H, CO2H), 12.02 (br, 1H, CONH), 11.83 (br, 1H, NH), 8.24 (s, 1H, H-8), 7.20 (s, 1H, H-3), 5.87 (m, 1H, vinyl-H), 5.05 (dd, 1H, vinyl-H), 4.99 (dd, 1H, vinyl-H), 4.03 (t, 2H, OCH2), 2.18 (q, 2H, allyl-CH2), 1.75 (m, 2H, CH2).

Workup

  1. concentrationThe solution was concentrated on a rotary evaporator
  2. customto remove THF
  3. customThe resulting mixture was partitioned between EtOAc (25 mL) and saturated aqueous NaCl (25 mL)
  4. customThe organic layer was separated
  5. waitto stand for 15 minutes
  6. customThe organic solution was decanted from some aqueous droplets
  7. customIt was then evaporated at reduced pressure
  8. customto give an orange solid
  9. customto give a slurry of an orange solid
  10. temperatureThe slurry was cooled on an ice bath for 10 minutes
  11. filtrationthe solid was collected by filtration
  12. washrinsing with ice-cold water (2×2 mL) and Et2O (2×2 mL)
  13. customThe solid was then dried under vacuum for 6 hours

Sources & evidence

ORD record
ord-e957de6ebdd547f0adfb7dd232d937d8
Source dataset
uspto-grants-2012_06
Patent number
US08198290B2

Reaction notes

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