Sodium Hydroxide → (s)-2-[2-Acetylamino-3-(4-cyanophenyl)acryloylamino]-2-cyclohexylacetic acid

HRID 7201

반응식

HRID 7201 반응식
[CH2:1]1[CH2:6][CH2:5][CH:4]([C@H:7]([NH2:11])[C:8]([OH:10])=[O:9])[CH2:3][CH2:2]1.[OH-].[Na+].[CH3:14][C:15]1[O:16][C:17](=[O:29])[C:18](=[CH:20][C:21]2[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][CH:22]=2)[N:19]=1>CC(C)=O>[C:15]([NH:19][C:18](=[CH:20][C:21]1[CH:22]=[CH:23][C:24]([C:25]#[N:26])=[CH:27][CH:28]=1)[C:17]([NH:11][C@@H:7]([CH:4]1[CH2:3][CH2:2][CH2:1][CH2:6][CH2:5]1)[C:8]([OH:10])=[O:9])=[O:29])(=[O:16])[CH3:14]

참가 물질

5

반응물 3

HCID 14798Sodium HydroxideHCID 3670804-((2-Methyl-5-oxo-4(5H)-oxazolylidene)methyl)benzonitrileHCID 736848(alphaS)-alpha-Aminocyclohexaneacetic acid

생성물 1

HCID 69513877(s)-2-[2-Acetylamino-3-(4-cyanophenyl)acryloylamino]-2-cyclohexylacetic acid

시약·촉매·용매 1

HCID 180Acetone용매

반응 조건

온도
35 °C

실험 절차

(S)-Cyclohexylglycine (3.14 kg, 20 mol) in acetone (70 l) was heated with stirring at 35° C. With stirring, 1 N aqueous sodium hydroxide solution (20 l) was then added over a period of 10 min. The mixture was heated to 40° C., and at an internal temperature of 40° C., solid 4-(2-methyl-5-oxooxazol-4-ylidenemethyl)benzonitrile (4.66 kg, 22 mol) was metered in in portions, with vigorous stirring, over 20 min. After the addition had been ended, the reaction mixture was stirred at an internal temperature of 40° C. for 1 h. The reaction solution was then filtered through a pressure nutsch covered with a Seitz filter K1000 and activated carbon (1 kg), and the filter residue was washed with 10 l of acetone. The filtrate was then cooled to 14° C. With stirring, 2N hydrochloric acid (about 10 l) was then added over a period of 10 min until a pH of 2.3 had been reached. Stirring was continued for 15 min, and the pH was readjusted using 2N HCl. Over a period of 20 min, the solution was then admixed with stirring with deionized water (160 l), whereupon the title compound precipitated. With stirring, the mixture was cooled to 0° C. and stirred at this temperature for 1 h. For isolation, the product was pumped onto a centrifuge, washed three times with water (10 l each), tumble-dried and dried at 40° C. under reduced pressure. Yield: 4.21 kg (11.4 mol, 57% of theory). M.p.: 196–198° C.; MS(ESI+): m/z=370.2 [M+H+]; 1H-NMR (200 MHz, DMSO-d6): δ=0.98–1.35 (m 1.48–1.90 (m, 6H), 1.99 (s, 3H), 4.20 (dd, 1H), 6.98 (s, 1H), 7.72 (d, 2H), 7.88 (d, 2H), 8.02 (d, 1H), 9.58 (s, 1H), 12.65 (br s, 1H).

후처리

  1. stirringWith stirring
  2. temperatureThe mixture was heated to 40° C.
  3. additionAfter the addition
  4. stirringthe reaction mixture was stirred at an internal temperature of 40° C. for 1 h
  5. filtrationThe reaction solution was then filtered through a pressure
  6. filtrationfilter
  7. washand activated carbon (1 kg), and the filter residue was washed with 10 l of acetone
  8. temperatureThe filtrate was then cooled to 14° C
  9. stirringWith stirring
  10. addition2N hydrochloric acid (about 10 l) was then added over a period of 10 min until a pH of 2.3
  11. stirringStirring
  12. waitOver a period of 20 min
  13. stirringwith stirring with deionized water (160 l), whereupon the title compound
  14. customprecipitated
  15. stirringWith stirring
  16. temperaturethe mixture was cooled to 0° C.
  17. stirringstirred at this temperature for 1 h
  18. washwashed three times with water (10 l each)
  19. customtumble-dried
  20. customdried at 40° C. under reduced pressure

출처 및 근거

ORD 기록
ord-f18edadf937d4e29883868e8d06ea4d1
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07084250B2

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