Propionyl chloride → HCID 89650692, compound

HRID 515947Notes

Reaction equation

HRID 515947 reaction equation
[CH:1]([O:4][C:5](=[O:41])[C@@H:6]([N:8]=[P:9]([O:11][C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14][C:13]=1[O:22][CH2:23][C@:24]1([F:40])[C@@H:28]([OH:29])[C@:27]([F:31])([CH3:30])[C@H:26]([N:32]2[CH:37]=[CH:36][C:35](=[O:38])[NH:34][C:33]2=[O:39])[O:25]1)=[O:10])[CH3:7])([CH3:3])[CH3:2].[C:42](Cl)(=[O:45])[CH2:43][CH3:44]>C1COCC1.CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[CH:1]([O:4][C:5](=[O:41])[C@@H:6]([N:8]=[P:9]([O:11][C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14][C:13]=1[O:22][CH2:23][C@:24]1([F:40])[C@@H:28]([O:29][C:42](=[O:45])[CH2:43][CH3:44])[C@:27]([F:31])([CH3:30])[C@H:26]([N:32]2[CH:37]=[CH:36][C:35](=[O:38])[NH:34][C:33]2=[O:39])[O:25]1)=[O:10])[CH3:7])([CH3:2])[CH3:3]

Participants

6

Reactant 2

HCID 62324Propionyl chlorideHCID 89651324HCID 89651324, compound

Product 1

HCID 89650692HCID 89650692, compoundYield 48%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-2-[[(2S,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2,4-difluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalen-1-yloxy)-phosphorylamino]-propionic acid isopropyl ester prepared in Example 2 (86 mg, 144 μmol) in THF (10 mL) were added propionyl chloride (66.6 mg, 720 μmol) and DMAP (87.9 mg, 720 μmol). The reaction mixture was stirred at room temperature for 5 h. The mixture was diluted with ethyl acetate, washed with water, brine. The organic layer was separated, dried over MgSO4, and concentrated. The residue was purified by flash chromatography (silica gel, 40 g, 0-15% MeOH in DCM) to give the title compound as white solid (45 mg, 48%).

Workup

  1. washwashed with water, brine
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography (silica gel, 40 g, 0-15% MeOH in DCM)

Sources & evidence

ORD record
ord-445f60c63a6a41808afdb9f6a9ab23b1
Source dataset
uspto-grants-2015_08
Patent number
US09108999B2

Reaction notes

Loading…