Citric Acid → HCID 51034413, compound

HRID 1777278Notes

Reaction equation

HRID 1777278 reaction equation
F[B-](F)(F)F.[N:6]1([O:15]C(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[Br:32][C:33]1[CH:38]=[C:37]([CH2:39][O:40][C:41]2[CH:60]=[CH:59][C:44]([C:45]([NH:47][CH2:48][C@H:49]([N:53]3[CH2:58][CH2:57][CH2:56][CH2:55][CH2:54]3)[C:50](O)=[O:51])=[O:46])=[CH:43][CH:42]=2)[CH:36]=[CH:35][N:34]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(=O)([O-])O.[Na+]>CN(C)C=O.O>[Br:32][C:33]1[CH:38]=[C:37]([CH2:39][O:40][C:41]2[CH:42]=[CH:43][C:44]([C:45]([NH:47][CH2:48][C@@H:49]([C:50](=[O:51])[NH:6][OH:15])[N:53]3[CH2:58][CH2:57][CH2:56][CH2:55][CH2:54]3)=[O:46])=[CH:59][CH:60]=2)[CH:36]=[CH:35][N:34]=1

Participants

8

Reactant 5

HCID 311Citric AcidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 86670458HCID 86670458, compound

Product 1

HCID 51034413HCID 51034413, compoundYield 10.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

130 mg (0.4 mmol) of O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate and 0.2 ml (1.2 mmol) of diisopropylethylamine are added to a solution of 185 mg (0.4 mmol) of (S)-3-[4-(2-bromopyridin-4-ylmethoxy)benzoylamino]-2-piperidin-1-ylpropanoic acid in 10 ml of dimethylformamide. After stirring for 20 minutes at ambient temperature, 65 mg (0.4 mmol) of O-tert-butyldimethysilylhydroxylamine diluted in 3 ml of dimethylformamide are added. The reaction medium is stirred at ambient temperature for 18 h, then hydrolysed with 1 ml of an aqueous solution of 5% citric acid and 2 ml of water. After stirring at ambient temperature for 1 h, the mixture is brought to pH=8 with a saturated aqueous solution of sodium hydrogen carbonate then extracted with ethyl acetate. The organic phase is washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, filtered and concentrated under vacuum. The crude product obtained is precipitated in an 8/2 heptane/ethyl acetate mixture then filtered. The residue obtained is recrystallized in ethyl acetate. 20 mg (10%) of 4-(2-bromopyridin-4-ylmethoxy)-N—((S)-2-hydroxycarbamoyl-2-piperidin-1-ylethyl)benzamide are obtained in the form of a pale-yellow solid having a melting point of 150° C.

Workup

  1. additionare added
  2. stirringThe reaction medium is stirred at ambient temperature for 18 h
  3. stirringAfter stirring at ambient temperature for 1 h
  4. extractionthen extracted with ethyl acetate
  5. washThe organic phase is washed with a saturated aqueous solution of sodium chloride
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe crude product obtained
  10. customis precipitated in an 8/2 heptane/ethyl acetate mixture
  11. filtrationthen filtered
  12. customThe residue obtained
  13. customis recrystallized in ethyl acetate

Sources & evidence

ORD record
ord-aec944dce047451fbce771492dfb0fcc
Source dataset
uspto-grants-2016_02
Patent number
US09266848B2

Reaction notes

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