Acetic Anhydride → HCID 178518031, compound

HRID 1467419Notes

Reaction equation

HRID 1467419 reaction equation
[NH2:1][C:2]1[C:10]([F:11])=[CH:9][CH:8]=[C:7]([F:12])[C:3]=1[C:4]([NH2:6])=[O:5].S([O-])([O-])(=O)=O.[NH4+].[NH4+].[CH2:20](OC(OCC)OCC)C.C(OC(=O)C)(=O)C>>[F:12][C:7]1[CH:8]=[CH:9][C:10]([F:11])=[C:2]2[C:3]=1[C:4]([OH:5])=[N:6][CH:20]=[N:1]2

Participants

5

Reactant 4

HCID 7918Acetic AnhydrideHCID 31214Ethyl orthoformateHCID 6097028Ammonium SulfateHCID 592230322-Amino-3,6-difluorobenzamide

Product 1

HCID 178518031HCID 178518031, compoundYield 92.3%

Conditions

Temperature
145 °C

Procedure

2-Amino-3,6-difluorobenzamide (2.0 g, 11.6 mmol), ammonium sulfate (0.15 g, 1.16 mmol), triethylorthoformate (4.3 g, 4.8 mL, 29.1 mmol) and acetic anhydride (3.0 g, 2.8 mL, 29.1 mmol) were combined in a 100 mL round bottomed flask and the mixture heated to 145° C. on a heating mantle, becoming nearly homogeneous around 90° C., then precipitating additional solid. After 1 h, the mixture was cooled to room temperature and diluted with water and stirred. The precipitated solids were collected by filtration, washed with water and dried to give 1.95 g of 5,8-difluoroquinazolin-4-ol as a white solid. A second crop of 0.13 g was collected from the cold concentrated filtrate, 98% overall. M.P. 257-258° C., LC/MS (ESI) m/z 182, 1H NMR (300 MHz, d6-DMSO) δ 12.48 (bs, 1H), 8.13 (s, 1H), 7.70 (m, 1H), 7.27 (m, 1H).

Workup

  1. custombecoming nearly homogeneous around 90° C.
  2. customprecipitating additional solid
  3. temperaturethe mixture was cooled to room temperature
  4. additiondiluted with water
  5. filtrationThe precipitated solids were collected by filtration
  6. washwashed with water
  7. customdried

Sources & evidence

ORD record
ord-45debce6544442cb813a4272ceaedaf4
Source dataset
uspto-grants-2015_04
Patent number
US09000162B2

Reaction notes

Loading…