Dimethylformamide → HCID 11234748, compound

HRID 1064762Notes

Reaction equation

HRID 1064762 reaction equation
[CH3:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][C:9]1[O:10][C:11]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=3)C(O)=O)=[CH:14][C:12]=2[CH:13]=1.C(Cl)(=O)[C:28](Cl)=[O:29].[CH3:33][N:34](C)[CH:35]=[O:36].Cl.CNOC>C(Cl)Cl.N1C=CC=CC=1>[CH3:28][O:29][N:34]([CH3:33])[C:35](=[O:36])[C:25]1[CH:24]=[CH:20][CH:19]=[C:18]([C:15]2[CH:16]=[CH:17][C:11]3[O:10][C:9]([CH2:8][CH2:7][N:3]4[CH2:4][CH2:5][CH2:6][C@H:2]4[CH3:1])=[CH:13][C:12]=3[CH:14]=2)[CH:26]=1

Participants

7

Reactant 4

HCID 6228Dimethylformamide2×HCID 65578Oxalyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 11163902HCID 11163902, compound

Product 1

HCID 11234748HCID 11234748, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

The product from Example 144 was suspended in CH2Cl2 (25 mL) and treated with 2 M oxalyl chloride in CH2Cl2 (3.0 mL, 6.0 mmol). After the bubbling had subsided, N,N-dimethylformamide (300 μL) was added slowly over 15 minutes. After an additional hour, more N,N-dimethylformamide (100 μL) was added. After another 30 minutes, the mixture was concentrated and dissolved into CH2Cl2 (5 mL). N,O-Dimethylhydroxylamine hydrochloride (488 mg, 5.0 mmol) and pyridine (1 mL) were added, the reaction flask was placed in a water bath, and the mixture was stirred overnight, concentrated, diluted with 1,2-dichloroethane (5 mL), heated at 85□C for four hours, concentrated, and partitioned between CH2Cl2 and water. Saturated aqueous NaHCO3 was added until the pH of the aqueous phase exceeded seven. Then the aqueous phase was separated and extracted with CH2Cl2. The combined organic phases were washed consecutively with water and brine, dried (Na2SO4), and chromatographed on silica with a gradient of 0 to 4% MeOH/CH2Cl2 to provide the title compound as a viscous brown syrup (60% yield from ester). 1HNMR (300 MHz, CD3OD) δ 1.19 (s, 3 H), 1.37-1.54 (m, 1 H), 1.73-1.88 (m, 2 H), 1.95-2.09 (m, 1 H), 2.27-2.39 (m, 1 H), 2.45-2.64 (m, 2 H), 2.95-3.17 (m, 2 H), 3.20-3.3 (m, 2 H), 3.39 (s, 3 H), 3.63 (s, 3 H), 6.62 (s, 1 H), 7.46-7.83 (m, 4 H), 7.73-7.81 (m, 2 H), 7.86 (s, 1 H).

Workup

  1. waitAfter an additional hour
  2. concentrationthe mixture was concentrated
  3. dissolutiondissolved into CH2Cl2 (5 mL)
  4. customthe reaction flask was placed in a water bath
  5. concentrationconcentrated
  6. additiondiluted with 1,2-dichloroethane (5 mL)
  7. temperatureheated at 85□C for four hours
  8. concentrationconcentrated
  9. custompartitioned between CH2Cl2 and water
  10. additionSaturated aqueous NaHCO3 was added until the pH of the aqueous phase
  11. customThen the aqueous phase was separated
  12. extractionextracted with CH2Cl2
  13. washThe combined organic phases were washed consecutively with water and brine
  14. dry with materialdried (Na2SO4)
  15. customchromatographed on silica with a gradient of 0 to 4% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-d760c1967f5d429eb8a4b71ce6c1c81e
Source dataset
uspto-grants-2005_11
Patent number
US06969730B2

Reaction notes

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