Hydrochloric Acid → HCID 86661642, 화합물

HRID 404551노트

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HRID 404551 반응식
[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].[Cl:14][C:15]1[CH:23]=[CH:22][C:18]([C:19](Cl)=[O:20])=[CH:17][N:16]=1.Cl>CC(OC)(C)C.C(O)C.O>[ClH:14].[Cl:14][C:15]1[N:16]=[CH:17][C:18]([C:19]([N:8]2[CH2:9][CH2:10][CH2:11][N:5]([CH:1]3[CH2:4][CH2:3][CH2:2]3)[CH2:6][CH2:7]2)=[O:20])=[CH:22][CH:23]=1

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 27821656-Chloronicotinoyl ChlorideHCID 574239531-Cyclobutyl-[1,4]diazepane

생성물 1

HCID 86661642HCID 86661642, 화합물

시약·촉매·용매 3

HCID 702Ethanol용매HCID 962Water용매HCID 15413tert-Butyl methyl ether용매

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온도
12.5 °C

실험 절차

A mixture of 1-cyclobutyl-[1,4]diazepane (prepared e.g. as in Example 13 above, 20.0 g, 129.7 mmol, 1.00 eq), water (95.2 g) and NaOH 30% aq. (34.6 g, 259.5 mmol, 2.00 eq) was cooled to 10-15° C. To the resulting mixture was added a solution of 6-chloronicotinic acid chloride (24.0 g, 136.4 mmol, 1.05 eq) in MTBE (250.0 g) at 10-15° C., over about 30-45 min, while stirring vigorously. The resulting emulsion was maintained at 10-20° C. for 45-60° C., before the layers were allowed to separate. The aqueous layer was removed and the organic layer washed with water (25.0 g). After removal of the aqueous layer, the organic layer was concentrated by distillation (140 g solvent are distilled off), ethanol (120 g) was added and additional solvent was distilled off (170 g solvent). The resulting solution was then heated to about 50-60° C. and HCl (gas, 4.8 g, 130.2 mmol) in ethanol (9.1 g) was added dropwise. The resulting solution was cooled to 43-45° C. and seeded crystals of the title compound. The product crystallized slowly at 43-45° C. when stirred for about 4-6 h. MTBE (60 g over 1.5-2 h, 120 g over 0.5-1 h) was added, the resulting mixture was then cooled to room temperature over 1-2 h and maintained for 1-2 h, before the title compound was isolated by filtration, washed with MTBE (2×40 g) and dried in vacuo at 65-75° C. for 2 days, to yield the title compound as a white solid.

후처리

  1. temperatureThe resulting emulsion was maintained at 10-20° C. for 45-60° C., before the layers
  2. customto separate
  3. customThe aqueous layer was removed
  4. washthe organic layer washed with water (25.0 g)
  5. customAfter removal of the aqueous layer
  6. concentrationthe organic layer was concentrated by distillation (140 g solvent are distilled off), ethanol (120 g)
  7. additionwas added
  8. distillationadditional solvent was distilled off (170 g solvent)
  9. temperatureThe resulting solution was then heated to about 50-60° C.
  10. temperatureThe resulting solution was cooled to 43-45° C.

출처 및 근거

ORD 기록
ord-2cfc776fe2ae4d30a1c486aaee6db880
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08748596B2

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