Methanol → HCID 9914765, compound

HRID 2120287Notes

Reaction equation

HRID 2120287 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:15]2[CH2:16][C@H:11]([CH2:12][CH2:13][C@@H:14]2[N:17]2[CH:25]=[N:24][C:23]3[C:18]2=[N:19][CH:20]=[N:21][C:22]=3[NH:26][C:27](=[O:36])[C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[CH2:10][C:9]1=[O:37])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C[O:41]CC1.[Li+].[OH-].CO>O>[C:1]([O:5][C:6]([NH:8][C@H:15]1[CH2:16][C@@H:11]([CH2:10][C:9]([OH:41])=[O:37])[CH2:12][CH2:13][C@@H:14]1[N:17]1[CH:25]=[N:24][C:23]2[C:18]1=[N:19][CH:20]=[N:21][C:22]=2[NH:26][C:27](=[O:36])[C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 15405474HCID 15405474, compound

Product 1

HCID 9914765HCID 9914765, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
0 °C

Procedure

A 500 ml two-necked round-bottomed flask was loaded with 5.25 g of PMBzBoc-A lactam 15f (10.36 mmol) and 200 ml of THF. After cooling to 0° C., a solution of 2.17 g of LiOH×H2O (51.8 mmol) in 50 ml of H2O was added dropwise over a period of 20 min. 30 ml of MeOH were then added, the ice bath was removed and the reaction mixture was stirred at room temperature for 1 h. An ion-exchange resin (Amberlite IR-120, H+ form) was then added until a pH of 7 was reached. The resin was removed by filtration and the solution was concentrated under reduced pressure to a volume of 100 ml. 200 ml of H2O were then added and a pH of 2 was adjusted by addition of 1 M aqueous HCl. The solution was extracted with EtOAc (3×200 ml) and the combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. The resulting residue was dissolved in 25 ml of hot MeOH. The product was then precipitated by addition of 10 ml of H2O. The precipitate was filtered, washed with H2O and dried over P4O10 to afford 1.95 g of 16. It was possible to obtain a further 0.57 g from the mother solution and the wash solutions to afford a total yield of 46%.

Workup

  1. customthe ice bath was removed
  2. additionAn ion-exchange resin (Amberlite IR-120, H+ form) was then added until a pH of 7
  3. customThe resin was removed by filtration
  4. concentrationthe solution was concentrated under reduced pressure to a volume of 100 ml
  5. addition200 ml of H2O were then added
  6. additiona pH of 2 was adjusted by addition of 1 M aqueous HCl
  7. extractionThe solution was extracted with EtOAc (3×200 ml)
  8. dry with materialthe combined organic extracts were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. dissolutionThe resulting residue was dissolved in 25 ml of hot MeOH
  12. customThe product was then precipitated by addition of 10 ml of H2O
  13. filtrationThe precipitate was filtered
  14. washwashed with H2O
  15. dry with materialdried over P4O10

Sources & evidence

ORD record
ord-6e9954403cf243a2aa925171702b87b6
Source dataset
uspto-grants-2004_02
Patent number
US06689884B1

Reaction notes

Loading…