Picolinic acid → HCID 18381987, compound

HRID 1599039Notes

Reaction equation

HRID 1599039 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 mL (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 1 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 4M HCl and diluted with methylene chloride. The aqueous layer was basified with 1N 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 4M 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-49c4048ed05f4262916bfe453b9a16f8
Source dataset
uspto-grants-1998_04
Patent number
US05739135

Reaction notes

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