Picolinic acid → HCID 18381987, compound

HRID 2297533Notes

Reaction equation

HRID 2297533 reaction equation
N1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7](O)=O.C([N:12]([CH2:15][CH3:16])[CH2:13][CH3:14])C.O=[C:18]1N(P(Cl)(N2CCOC2=O)=O)CCO1.Cl.O([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1/[CH:46]=[CH:47]/[CH2:48][N:49]1[CH2:54][CH2:53][CH:52]([N:55]2CC3C(=CC=CC=3)[C:56]2=[O:64])[CH2:51][CH2:50]1)C1C=CC=CC=1>C(Cl)Cl>[C:2]1([CH:46]([C:41]2[CH:40]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:47][CH2:48][N:49]2[CH2:54][CH2:53][CH:52]([NH:55][C:56]([C:15]3[CH:16]=[CH:18][CH:14]=[CH:13][N:12]=3)=[O:64])[CH2:51][CH2:50]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 1018Picolinic acidHCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 131720602HCID 131720602, compound

Product 1

HCID 18381987HCID 18381987, compoundYield 85.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred suspension of 199 mg (1.62 mmol) of picolinic acid in 2.5 mL of methylene chloride at 0° C. was added 225 μL (1.62 mmol) of triethylamine. After all the solids had dissolved, the solution was treated with 412 mg (1.62 mmol) of bis(2-oxo-3-oxazolidinyl)phosphinic chloride, and stirred for 30 minutes. A methylene chloride solution of 535 mg (1.62 mmol) of compound E from Example 10 was converted to the free amine by washing with sodium bicarbonate and concentrating the organic layer to a brown oil which was redissolved in 1 mL of dry methylene chloride and added to the reaction mixture. After stirring at room temperature for 16 hours, the reaction was quenched with water and 4 M HCl and diluted with methylene chloride. The aqueous layer was basified with 1 N KOH and extracted two times. The combined organics were dried (sodium sulfate) and concentrated to provide 554 mg of a brown oil. The crude product was purified by flash chromatography on silica gel eluted with 98:2 ethyl acetate/methanol to provide 316 mg (58%) of compound A as a brown glass.

Workup

  1. dissolutionAfter all the solids had dissolved
  2. washby washing with sodium bicarbonate
  3. concentrationconcentrating the organic layer to a brown oil which
  4. dissolutionwas redissolved in 1 mL of dry methylene chloride
  5. additionadded to the reaction mixture
  6. stirringAfter stirring at room temperature for 16 hours
  7. customthe reaction was quenched with water and 4 M HCl
  8. additiondiluted with methylene chloride
  9. extractionextracted two times
  10. dry with materialThe combined organics were dried (sodium sulfate)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-4a055eb622a34b3cb03272e06350af00
Source dataset
uspto-grants-2002_12
Patent number
US06492365B1

Reaction notes

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