Oxalyl chloride → HCID 22905326, compound

HRID 1488681Notes

Reaction equation

HRID 1488681 reaction equation
C(Cl)(=O)C(Cl)=O.[C:7]([C:9]1[CH:28]=[CH:27][C:12]([CH2:13][O:14][C:15]2[CH:16]=[CH:17][C:18]([N+:24]([O-:26])=[O:25])=[C:19]([CH:23]=2)[C:20]([OH:22])=O)=[CH:11][CH:10]=1)#[N:8].Cl.[CH2:30]([O:32][C:33](=[O:37])[CH2:34][CH2:35][NH2:36])[CH3:31].C(=O)(O)[O-].[Na+]>C1C=CC=CC=1.O1CCCC1.O.CN(C)C=O>[CH2:30]([O:32][C:33](=[O:37])[CH2:34][CH2:35][NH:36][C:20](=[O:22])[C:19]1[CH:23]=[C:15]([O:14][CH2:13][C:12]2[CH:11]=[CH:10][C:9]([C:7]#[N:8])=[CH:28][CH:27]=2)[CH:16]=[CH:17][C:18]=1[N+:24]([O-:26])=[O:25])[CH3:31]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 516892Sodium BicarbonateHCID 229049555-(4-Cyanobenzyloxy)-2-nitrobenzoic acid

Product 1

HCID 22905326HCID 22905326, compoundYield 91.1%

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 6228DimethylformamideSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
60 °C

Procedure

Oxalyl chloride (5.70 mL, 65.4 mmol) was added slowly to a rapidly stirred suspension of 14.6 g (48.9 mmol) of 5-(4-cyanobenzyloxy)-2-nitrobenzoic acid and 2 mL of dimethylformamide in 100 mL of benzene. When gas evolution ceased, the solution was heated briefly to 60° C., concentrated in vacuo, and redissolved in 75 mL of tetrahydrofuran. This solution was added dropwise to a rapidly stirred suspension of 8.50 g (55.3 mmol) of b-alanine ethyl ester hydrochloride and 21.1 g (251 mmol) of sodium bicarbonate in 325 mL of 2:1 tetrahydrofuran/water at 0° C. The mixture was warmed to ambient temperature for 12 h and the tetrahydrofuran was removed in vacuo. The residue was partitioned between ethyl acetate and 1N sodium bicarbonate and the aqueous phase was separated and extracted with ethyl acetate. The combined organics were washed with 1N sodium hydrogen sulfate, water, brine, dried over anhydrous magnesium sulfate, and concentrated to give 17.7 g (91%) of N-(5-(4-cyanobenzyloxy)-2-nitrobenzoyl)-b-alanine ethyl ester as a tan powder. 1H NMR (300 MHz, CDCl3) d 8.11 (1H, d, J=8.3 Hz, O-Ar-H), 7.71 (2H, d, J=8.3 Hz, NC-Ar-H2), 7.52 (2H, d, J=8.3 Hz, NC-Ar-H2), 7.01 (2H, m, O-Ar-H2), 6.50 (1H, bt, J=5.9 Hz, N-H), 5.21 (2H, s, ArCH2O), 4.14 (2H, q, J=7.3 Hz, OCH2 CH3), 3.69 (2H, bq, J=5.8 Hz, NCH2CH2), 2H, t, J=5.8 Hz, NCH2CH2), 1.26 (3H, t, J=7.3 Hz, OCH2CH3); Exact mass (FAB M+H+) calcd for C20H20N3O6 : 398.1352; Found: 398.1343.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionredissolved in 75 mL of tetrahydrofuran
  3. temperatureThe mixture was warmed to ambient temperature for 12 h
  4. customthe tetrahydrofuran was removed in vacuo
  5. customThe residue was partitioned between ethyl acetate and 1N sodium bicarbonate
  6. customthe aqueous phase was separated
  7. extractionextracted with ethyl acetate
  8. washThe combined organics were washed with 1N sodium hydrogen sulfate, water, brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-67c245abc66e4049b1917a829c01520b
Source dataset
uspto-grants-1997_10
Patent number
US05674865

Reaction notes

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