Ammonium Chloride → 5-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide

HRID 46316

반응식

HRID 46316 반응식
[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][NH:6][C:7]1[S:8][CH:9]=[N:10][N:11]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:28][C:29]1[C:30]([F:40])=[CH:31][C:32]([F:39])=[C:33]([S:35](Cl)(=[O:37])=[O:36])[CH:34]=1.[Cl-].[NH4+]>CC1CCCO1.O>[Cl:28][C:29]1[C:30]([F:40])=[CH:31][C:32]([F:39])=[C:33]([S:35]([N:6]([CH2:5][C:4]2[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:3]=2[O:2][CH3:1])[C:7]2[S:8][CH:9]=[N:10][N:11]=2)(=[O:37])=[O:36])[CH:34]=1

참가 물질

7

반응물 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 27735275-Chloro-2,4-difluorobenzenesulphonyl chlorideHCID 58042278N-(2,4-dimethoxybenzyl)-1,3,4-thiadiazol-2-amine

생성물 1

HCID 580422535-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide수율 58.5%

시약·촉매·용매 2

HCID 962Water용매HCID 73012-Methyltetrahydrofuran용매2회

반응 조건

온도
15 °C

실험 절차

N-(2,4-Dimethoxybenzyl)-1,3,4-thiadiazol-2-amine (Preparation 248, 203.4 g, 0.809 moles) was dissolved in 2-methyltetrahydrofuran (1.63 L) and the yellow suspension was cooled to −38° C. to −45° C. Lithium bis(trimethylsilyl)amide (890 mL of 1 molar solution in tetrahydrofuran, 0.890 moles) was added slowly over 15 minutes keeping the temperature between −38° C. and −45° C. to give an orange suspension. This orange suspension was stirred at −38° C. to −45° C. for 45 minutes and then a solution of 5-chloro-2,4-difluorobenzenesulfonyl chloride, (200 g, 0.809 moles) in 2-methyltetrahydrofuran (407 mL) was added slowly over 20 minutes keeping the temperature between −38° C. and −45° C. to give an orange suspension. The mixture was stirred whist warming to 15° C. over 1 hour. The reaction was quenched by adding a solution of ammonium chloride (203.4 g, 3.80 moles) in water (1.02 L) and stirred vigorously for 5 minutes. The stirring was stopped and the phases allowed to separate. The lower layer was removed and the organic layer was washed with water (813.6 mL). The organic layer was concentrated in vacuo to give an orange solid which was triturated with isopropyl acetate (1.22 L) to give the title compound as a yellow-orange solid (218.6 g).

후처리

  1. temperaturethe yellow suspension was cooled to −38° C. to −45° C
  2. customthe temperature between −38° C. and −45° C.
  3. customto give an orange suspension
  4. customthe temperature between −38° C. and −45° C.
  5. customto give an orange suspension
  6. stirringThe mixture was stirred whist
  7. customThe reaction was quenched
  8. stirringstirred vigorously for 5 minutes
  9. customto separate
  10. customThe lower layer was removed
  11. washthe organic layer was washed with water (813.6 mL)
  12. concentrationThe organic layer was concentrated in vacuo
  13. customto give an orange solid which
  14. customwas triturated with isopropyl acetate (1.22 L)

출처 및 근거

ORD 기록
ord-e9ef8fdc7ee343efa8059b5f3757afb2
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541588B2

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