Methanol → HCID 89650724, compound

HRID 515942Notes

Reaction equation

HRID 515942 reaction equation
[F:1][C@:2]1([CH3:19])[C@H:6]([OH:7])[C@@:5]([F:10])([CH2:8][OH:9])[O:4][C@H:3]1[N:11]1[CH:16]=[CH:15][C:14](=[O:17])[NH:13][C:12]1=[O:18].C([Mg]Cl)(C)(C)C.Cl[C:27]1[CH:44]=[CH:43][CH:42]=[CH:41][C:28]=1[O:29][P:30](=[N:32][C@@H:33]([CH3:40])[C:34]([O:36][CH:37]([CH3:39])[CH3:38])=[O:35])=[O:31].CO>C1COCC1>[CH:37]([O:36][C:34](=[O:35])[C@@H:33]([N:32]=[P:30]([O:29][C:28]1[CH:41]=[CH:42][CH:43]=[CH:44][C:27]=1[O:9][CH2:8][C@:5]1([F:10])[C@@H:6]([OH:7])[C@:2]([F:1])([CH3:19])[C@H:3]([N:11]2[CH:16]=[CH:15][C:14](=[O:17])[NH:13][C:12]2=[O:18])[O:4]1)=[O:31])[CH3:40])([CH3:38])[CH3:39]

Participants

6

Reactant 4

HCID 887MethanolHCID 66713330HCID 66713330, compound2×HCID 89650994HCID 89650994, compoundHCID 178418310HCID 178418310, compound2×

Product 1

HCID 89650724HCID 89650724, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent5×

Procedure

To a solution of chiral 1-((2R,3R,4S,5S)-3,5-difluoro-4-hydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione (42 mg, 151 μmol) prepared in Preparation 6 in THF (8.00 ml) was added a THF solution (Aldrich, 1 M) of tert-butylmagnesium chloride (377 μl, 377 μmol) dropwise. The mixture was stirred at room temperature for 15 min. followed by the addition of THF solution (0.5 M) of (2S)-isopropyl 2-(chloro(phenoxy)phosphorylamino)propanoate (755 μl, 377 μmol). The reaction mixture was stirred at room temperature for 1 hr, followed by the addition of THF solution (Aldrich, 1 M) of tert-butylmagnesium chloride (189 μl, 189 μmol) and THF solution (0.5 M) of (2S)-isopropyl 2-(chloro(phenoxy)phosphorylamino)propanoate (378 μl, 189 μmol). The reaction mixture was then stirred at room temperature for 2 h. Methanol (2 mL) was added to quench the reaction, The mixture was purified by flash chromatography (silica gel, 0-15% MeOH in DCM) and dried in vacuo to give the title compound as a light-yellow solid (18 mg, 22%).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 1 hr
  2. stirringThe reaction mixture was then stirred at room temperature for 2 h
  3. customto quench
  4. customthe reaction
  5. customThe mixture was purified by flash chromatography (silica gel, 0-15% MeOH in DCM)
  6. customdried in vacuo

Sources & evidence

ORD record
ord-ea3aeebcac5c41709dae26663e6e585a
Source dataset
uspto-grants-2015_08
Patent number
US09108999B2

Reaction notes

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