Tetrahydro-4H-pyran-4-one → HCID 11650188, compound

HRID 2099353Notes

Reaction equation

HRID 2099353 reaction equation
[Cl:1][C:2]1[CH:34]=[CH:33][C:5]([CH2:6][C@H:7]([C:9]([N:11]2[CH:16]3[CH2:17][CH2:18][CH:12]2[CH2:13][CH:14]([N:19]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[C:20]([N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])=[O:21])[CH2:15]3)=[O:10])[NH2:8])=[CH:4][CH:3]=1.[O:35]1[CH2:40][CH2:39][C:38](=O)[CH2:37][CH2:36]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C@H:7]([C:9]([N:11]2[CH:16]3[CH2:17][CH2:18][CH:12]2[CH2:13][CH:14]([N:19]([CH:27]2[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]2)[C:20]([N:22]([CH2:23][CH3:24])[CH2:25][CH3:26])=[O:21])[CH2:15]3)=[O:10])[NH:8][CH:38]2[CH2:39][CH2:40][O:35][CH2:36][CH2:37]2)=[CH:33][CH:34]=1

Participants

5

Reactant 3

HCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 68829063HCID 68829063, compound

Product 1

HCID 11650188HCID 11650188, compoundYield 65.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

0.30 g of the N-[8-(4-chloro-D-phenylalanyl)-8-azabicyclo[3.2.1]oct-3-yl]-N-cyclohexyl-N′,N′-diethylurea endo compound, obtained in step 1.5, is dissolved in 3 ml of dichloromethane under N2 in the presence of 0.061 g of tetrahydro-4H-pyran-4-one and of 0.17 g of sodium triacetoxyborohydride. The reaction medium is stirred at ambient temperature for 3 days. After evaporation and hydrolysis with a saturated aqueous sodium hydrogen carbonate solution, extraction is carried out with ethyl acetate until the aqueous phase is completely depleted. The organic phase is washed with H2O and then with a saturated aqueous sodium chloride solution. Drying over MgSO4 and concentration to dryness are carried out. The crude is chromatographed on silica gel, elution being carried out with a 99/1 and then 98/2 mixture of dichloromethane and methanol. 0.23 g of N-{8-[4-chloro-N-(tetrahydro-2H-pyran-4-yl)-D-phenylalanyl]-8-azabicyclo[3.2.1]oct-3-yl}-N-cyclohexyl-N′,N′-diethylurea is then obtained.

Workup

  1. customobtained in step 1.5
  2. customAfter evaporation and hydrolysis
  3. extractionwith a saturated aqueous sodium hydrogen carbonate solution, extraction
  4. washThe organic phase is washed with H2O
  5. dry with materialDrying over MgSO4 and concentration to dryness
  6. customThe crude is chromatographed on silica gel, elution
  7. addition98/2 mixture of dichloromethane and methanol

Sources & evidence

ORD record
ord-a8adbb1096fa4d39909fe2338203a82b
Source dataset
uspto-grants-2009_08
Patent number
US07569582B2

Reaction notes

Loading…