Hydrogen Peroxide → HCID 58304250, 화합물

HRID 1941785노트

반응식

HRID 1941785 반응식
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:18])=[C:6]([C@:8]2([CH3:17])[C:13]([F:15])([F:14])[CH2:12][O:11][C:10]([NH2:16])=[N:9]2)[CH:7]=1.[I-:19].[NH4+].OO>C(O)(=O)C>[NH2:1][C:2]1[C:3]([I:19])=[CH:4][C:5]([F:18])=[C:6]([C@:8]2([CH3:17])[C:13]([F:14])([F:15])[CH2:12][O:11][C:10]([NH2:16])=[N:9]2)[CH:7]=1

참가 물질

5

반응물 3

HCID 784Hydrogen Peroxide2회HCID 25487Ammonium iodide2회HCID 58304207(R)-4-(5-amino-2-fluoro-phenyl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine

생성물 1

HCID 58304250HCID 58304250, 화합물

시약·촉매·용매 1

HCID 176Acetic Acid용매

실험 절차

Intermediate XI-3 (R2a=F; R2b=I; R3=Me; R4 and R5=H): A solution of (R)-4-(5-amino-2-fluoro-phenyl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (intermediate XI-1) (500 mg, 1.9 mmol) and ammonium iodide (308 mg, 2.1 mmol) in acetic acid (9.6 ml) was treated at room temperature with an aqueous solution of hydrogen peroxide (35%, 0.19 ml, 2.1 mmol). After stirring overnight 50% of the starting material was left. Another equivalent of ammonium iodide and hydrogen peroxide was added and stirring continued at room temperature overnight. For the workup, the reaction mixture was filtered, the filtrate treated with sodium thiosulphate, then extracted with ethyl acetate (3×). The combined organic layers were washed with a saturated solution of sodium hydrogen carbonate, then dried over sodium sulphate and evaporated at reduced pressure. In order to eliminate residual acetic acid, the crude product was dissolved in dichloromethane and extracted again with a saturated solution of sodium hydrogen carbonate. The crude product was purified by chromatography on an Isolute flash NH2 column using a gradient of heptane/ethyl acetate=100/0 to 0/100 as the eluent. The (R)-4-(5-amino-2-fluoro-4-iodo-phenyl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine was obtained as a yellow solid (415 mg, 56% of theory). MS (ISP): m/z=386.0 [M+H]+.

후처리

  1. waitwas left
  2. filtrationFor the workup, the reaction mixture was filtered
  3. additionthe filtrate treated with sodium thiosulphate
  4. extractionextracted with ethyl acetate (3×)
  5. washThe combined organic layers were washed with a saturated solution of sodium hydrogen carbonate
  6. dry with materialdried over sodium sulphate
  7. customevaporated at reduced pressure
  8. dissolutionthe crude product was dissolved in dichloromethane
  9. extractionextracted again with a saturated solution of sodium hydrogen carbonate
  10. customThe crude product was purified by chromatography on an Isolute flash NH2 column

출처 및 근거

ORD 기록
ord-f74d7e93695a4098aad9414dea8907cf
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389513B2

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