Diethyl Ether → 2,2-dimethylpropionic Acid 4-(dimethylamino-methyleneamino)-5-fluoro-pyrimidin-2-yloxymethyl Ester

HRID 1500034Notes

Reaction equation

HRID 1500034 reaction equation
[F:1][C:2]1[C:3]([N:9]=[CH:10][N:11]([CH3:13])[CH3:12])=[N:4][C:5]([OH:8])=[N:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:20]([O:26][CH2:27]Cl)(=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22].C(OCC)C>CN(C=O)C>[CH3:12][N:11]([CH:10]=[N:9][C:3]1[C:2]([F:1])=[CH:7][N:6]=[C:5]([O:8][CH2:27][O:26][C:20](=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22])[N:4]=1)[CH3:13]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 10796Cesium carbonateHCID 87885Chloromethyl pivalateHCID 178484257HCID 178484257, compound

Product 1

HCID 578184502,2-dimethylpropionic Acid 4-(dimethylamino-methyleneamino)-5-fluoro-pyrimidin-2-yloxymethyl EsterYield 9.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N′-(5-Fluoro-2-hydroxypyrimidin-4-yl)-N,N-dimethylformamidine (100 mg, 0.54 mmol), cesium carbonate (196 mg, 0.60 mmol), and chloromethyl pivalate (90 mg, 0.6 mmol) were shaken together in DMF (3 mL) at ambient temperature for 16 hours. The reaction mixture was partitioned between ethyl acetate and water, dried over magnesium sulfate, filtered and evaporated to yield a colorless oil which was treated with diethyl ether (3-4 mL) to produce a solid. The solid was removed and the ether solution was placed onto a silica gel column and eluted with ethyl acetate in petroleum ether (0-50% gradient) to isolate 14 mg, 0.05 mmol (9%) of the title compound as a white solid: mp 86-88° C.; 1H NMR (CDCl3) δ 8.73 (s, 1H), 8.06 (d, J=2.6 Hz, 1H), 6.04 (s, 2H), 3.20 (s, 3H), 3.18 (s, 3H), 1.16 (s, 9H); HPLC-MS (ESI) m/z 299 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customto yield a colorless oil which
  6. customto produce a solid
  7. customThe solid was removed
  8. washeluted with ethyl acetate in petroleum ether (0-50% gradient)

Sources & evidence

ORD record
ord-e8074d1e031845f480246c72e4e159bc
Source dataset
uspto-grants-2015_12
Patent number
US09204653B2

Reaction notes

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