Sodium Sulfate → ethyl 5-(benzyloxy)-4-fluoro-2-(tetrahydro-2H-pyran-4-ylamino)benzoate

HRID 1022483Notes

Reaction equation

HRID 1022483 reaction equation
[NH2:1][C:2]1[CH:12]=[C:11]([F:13])[C:10]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].[O:22]1[CH2:27][CH2:26][C:25](=O)[CH2:24][CH2:23]1.[O-]S([O-])(=O)=O.[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[CH2:15]([O:14][C:10]1[C:11]([F:13])=[CH:12][C:2]([NH:1][CH:25]2[CH2:26][CH2:27][O:22][CH2:23][CH2:24]2)=[C:3]([CH:9]=1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 24436Sodium SulfateHCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 61994641Ethyl 2-amino-5-(benzyloxy)-4-fluorobenzoate

Product 1

HCID 67495078ethyl 5-(benzyloxy)-4-fluoro-2-(tetrahydro-2H-pyran-4-ylamino)benzoateYield 77.8%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 10.5 g of the compound obtained in Step 4.2, 29.07 g of tetrahydro-4H-pyran-4-one and 51.56 g of Na2SO4 in 360 ml of acetic acid is stirred overnight at room temperature. 34.62 g of sodium triacetoxyborohydride are then added and the mixture is stirred for 3 hours at room temperature. The resulting mixture is evaporated under reduced pressure and the residue is taken up in EtOAc. This solution is washed with water and then 4 times with saturated aqueous NaHCO3 solution. The resulting solution is dried over MgSO4 and filtered, and the filtrate is evaporated under reduced pressure. The residue is chromatographed on silica gel, eluting with a PE/EtOAc mixture from (100/0, v/v) to (50/50, v/v) to give 10.55 g of the expected product.

Workup

  1. stirringthe mixture is stirred for 3 hours at room temperature
  2. customThe resulting mixture is evaporated under reduced pressure
  3. washThis solution is washed with water
  4. dry with materialThe resulting solution is dried over MgSO4
  5. filtrationfiltered
  6. customthe filtrate is evaporated under reduced pressure
  7. customThe residue is chromatographed on silica gel
  8. washeluting with a PE/EtOAc mixture from (100/0

Sources & evidence

ORD record
ord-fd12873129e4484fbcfe4f95c6a58609
Source dataset
uspto-grants-2014_05
Patent number
US08722659B2

Reaction notes

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