Oxalyl chloride → HCID 58980664, compound

HRID 735788Notes

Reaction equation

HRID 735788 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:17]=1[N:16]([CH3:18])[C:15]([C:19]([OH:21])=O)=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.C(N(CC)C(C)C)(C)C.[C:37]([C:41]1[CH:46]=[C:45]([NH2:47])[C:44]([O:48][CH3:49])=[CH:43][N:42]=1)([CH3:40])([CH3:39])[CH3:38].C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C)C=O>[C:37]([C:41]1[CH:46]=[C:45]([NH:47][C:19]([C:15]2[N:16]([CH3:18])[C:17]3[C:13]([CH:14]=2)=[CH:12][CH:11]=[CH:10][C:9]=3[O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:21])[C:44]([O:48][CH3:49])=[CH:43][N:42]=1)([CH3:40])([CH3:38])[CH3:39]

Participants

8

Reactant 5

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 23540367HCID 23540367, compoundHCID 58980614HCID 58980614, compound

Product 1

HCID 58980664HCID 58980664, compoundYield 100.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a slurry of 7-benzyloxy-1-methyl-1H-indole-2-carboxylic acid (163 mg, 0.58 mmol) in methylene chloride (2 mL) at 0° C. was added oxalyl chloride (72 microL, 0.84 mmol) followed by a drop of N,N-dimethylformamide. The solution immediately bubbled and became clear after a period of 0.75 h. The mixture was concentrated and redissolved in methylene chloride (1.5 mL). The acid chloride solution was added to a solution of N,N-diisopropylethylamine (202 microL, 1.16 mmol) and 2-tert-butyl-5-methoxy-pyridin-4-ylamine (95 mg, 0.52 mmol) in methylene chloride (1.5 mL). The solution was stirred at room temperature for 3 h then poured onto saturated aqueous NaHCO3. The aqueous layer was extracted with methylene chloride and the combined extracts were washed with saturated aqueous NaHCO3, followed by saturated aqueous KH2PO4, and again with saturated aqueous NaHCO3. The organic extracts were dried over sodium sulfate, filtered through a plug of silica-gel with diethyl ether, and concentrated in vacuo to provide pure 7-benzyloxy-1-methyl-1H-indole-2-carboxylic acid (2-tert-butyl-5-methoxy-pyridin-4-yl)-amide (231 mg, 99%) as a white solid.

Workup

  1. customThe solution immediately bubbled
  2. concentrationThe mixture was concentrated
  3. dissolutionredissolved in methylene chloride (1.5 mL)
  4. extractionThe aqueous layer was extracted with methylene chloride
  5. washthe combined extracts were washed with saturated aqueous NaHCO3
  6. dry with materialThe organic extracts were dried over sodium sulfate
  7. filtrationfiltered through a plug of silica-gel with diethyl ether
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b1d6e55b064d4f598e89a7f740c3ad5f
Source dataset
uspto-grants-2009_09
Patent number
US07592332B2

Reaction notes

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