Dimethylformamide → Chroman-2-carboxamide

HRID 1071161Notes

Reaction equation

HRID 1071161 reaction equation
C(Cl)(=O)C(Cl)=O.[O:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10][CH2:9][CH:8]1[C:17]([OH:19])=O.C[N:21](C)C=O>O1CCCC1.O>[O:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10][CH2:9][CH:8]1[C:17]([NH2:21])=[O:19]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 27236653,4-dihydro-2H-1-benzopyran-2-carboxylic acid

Product 1

HCID 18621312Chroman-2-carboxamideYield 97%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Oxalyl chloride (11.0 mL, 126 mmol) was added dropwise to a cooled (0° C.) solution of the compound from Example 20 (15 g, 84.3 mmol) and N,N-dimethylformamide (1 mL) in tetrahydrofuran (250 mL). Upon completion of gas evolution the mixture was warmed to room temperature and concentrated in vacuo. The residue was dissolved in tetrahydrofuran (450 mL). The solution was cooled to −78° C. and ammonia condensed onto the mixture. After 30 minutes the mixture was warmed to room temperature, diluted with water, and extracted with ethyl acetate (2×). The combined organic phase was washed with saturated aqueous sodium chloride solution (2×), dried (MgSO4), and concentrated to give a solid. The solid was triturated with 1:1 diethyl ether/hexanes and dried at 50° C. in vacuo to give a colorless solid (14.5 g, 97%). Mp 125-127° C.; 1H NMR (acetone-d6, 300 MHz) δ 7.08 (m, 3H), 6.86 (m, 2H), 6.75 (br s, 1H), 4.47 (dd, 9.2 Hz, 2.9 Hz, 1H), 2.76 (m, 2H), 2.28 (m, 1H), 0.96 (m, 1H).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in tetrahydrofuran (450 mL)
  3. temperatureThe solution was cooled to −78° C.
  4. customammonia condensed onto the mixture
  5. temperatureAfter 30 minutes the mixture was warmed to room temperature
  6. extractionextracted with ethyl acetate (2×)
  7. washThe combined organic phase was washed with saturated aqueous sodium chloride solution (2×)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customto give a solid
  11. customThe solid was triturated with 1:1 diethyl ether/hexanes
  12. customdried at 50° C. in vacuo

Sources & evidence

ORD record
ord-760206fa344b41978d5989183e09a722
Source dataset
uspto-grants-2005_06
Patent number
US06903218B2

Reaction notes

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