Dimethylformamide → HCID 86760228, compound

HRID 11932Notes

Reaction equation

HRID 11932 reaction equation
P(Cl)(Cl)(Cl)=O.C([O:10][C:11]([N:13]1[CH2:25][C@@H:24]([CH3:26])[N:23]2[C:15](=[CH:16][C:17]3[C:22]2=[N:21][C:20]([Cl:27])=[CH:19][CH:18]=3)[CH2:14]1)=[O:12])(C)(C)C.CN(C)[CH:30]=[O:31]>>[Cl:27][C:20]1[N:21]=[C:22]2[C:17](=[CH:18][CH:19]=1)[C:16]([CH:30]=[O:31])=[C:15]1[N:23]2[C@H:24]([CH3:26])[CH2:25][N:13]([C:11]([OH:10])=[O:12])[CH2:14]1

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 86590114(R)-6-chloro-4-methyl-3,4-dihydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

Product 1

HCID 86760228HCID 86760228, compoundYield 55.2%

Procedure

N,N-Dimethylformamide (10 ml) was cooled to 1 deg C. and treated dropwise with 5.1 ml (56.0 mmol) phosphorus oxychloride. After the addition the temperature was again cooled to 1 deg C. and a solution of 1.0 g (3.11 mmol) (R)-6-chloro-4-methyl-3,4-dihydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester in (Example 2, intermediate a) in 10 ml N,N-dimethylformamide was added. The cooling bath was removed and after 1.5 h at room temperature the reaction mixture was poured into saturated aqueous sodium bicarbonate solution and was extracted three times with ethyl acetate. The combined organic phases were washed with water and brine, dried over magnesium sulfate, filtered and evaporated. The residue was purified by chromatography on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:3) as eluant to yield the desired compound as a yellow foam (55.2%).

Workup

  1. additionAfter the addition the temperature
  2. temperaturewas again cooled to 1 deg C
  3. customThe cooling bath was removed and after 1.5 h at room temperature the reaction mixture
  4. additionwas poured into saturated aqueous sodium bicarbonate solution
  5. extractionwas extracted three times with ethyl acetate
  6. washThe combined organic phases were washed with water and brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by chromatography on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:3) as eluant

Sources & evidence

ORD record
ord-d9c2ecbcaca9440d991fda79c7080583
Source dataset
uspto-grants-2006_08
Patent number
US07098337B2

Reaction notes

Loading…