3-Hydroxy-5-(2-oxopyrrolidin-1-yl)benzoic acid → (2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-hydroxy-5-(2-oxopyrrolidin-1-yl)benzamido)propyl)-4-propoxypyrrolidine-1-carboxylate

HRID 1014874

반응식

HRID 1014874 반응식
[Si:1]([O:8][C@H:9]([C@H:34]1[CH2:38][C@@H:37]([O:39][CH2:40][CH2:41][CH3:42])[CH2:36][N:35]1[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[C@@H:10]([NH:20]C(=O)C1C=C(C)C=C(C(OC)=O)C=1)[CH2:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[OH:50][C:51]1[CH:52]=[C:53]([CH:57]=[C:58]([N:60]2[CH2:64][CH2:63][CH2:62][C:61]2=[O:65])[CH:59]=1)[C:54]([OH:56])=O.BrC1C=C(C=C(C(OC)=O)C=1)C(N[C@@H](CC1C=C(F)C=C(F)C=1)[C@@H]([C@H]1C[C@@H](OCCC)CN1C(OC(C)(C)C)=O)O[Si](C(C)(C)C)(C)C)=O.N([O-])=O.[Na+]>Cl.O.CO>[Si:1]([O:8][C@H:9]([C@H:34]1[CH2:38][C@@H:37]([O:39][CH2:40][CH2:41][CH3:42])[CH2:36][N:35]1[C:43]([O:45][C:46]([CH3:47])([CH3:49])[CH3:48])=[O:44])[C@@H:10]([NH:20][C:54](=[O:56])[C:53]1[CH:57]=[C:58]([N:60]2[CH2:64][CH2:63][CH2:62][C:61]2=[O:65])[CH:59]=[C:51]([OH:50])[CH:52]=1)[CH2:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

참가 물질

8

반응물 4

HCID 222530273-Hydroxy-5-(2-oxopyrrolidin-1-yl)benzoic acidHCID 23668193Sodium NitriteHCID 67315749(2R,4R)-tert-butyl 2-((1S,2S)-2-(3-bromo-5-(methoxycarbonyl)benzamido)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylateHCID 67316204(2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-(methoxycarbonyl)-5-methylbenzamido)propyl)-4-propoxypyrrolidine-1-carboxylate

생성물 1

HCID 59346851(2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)-2-(3-hydroxy-5-(2-oxopyrrolidin-1-yl)benzamido)propyl)-4-propoxypyrrolidine-1-carboxylate

시약·촉매·용매 3

HCID 313Hydrochloric Acid용매2회HCID 887Methanol용매HCID 962Water용매

반응 조건

온도
0 °C

실험 절차

Step I (4): 3-Hydroxy-5-(2-oxopyrrolidin-1-yl)benzoic acid. To a solution of 3-amino-5-(2-oxopyrrolidin-1-yl)benzoic acid (Step I (3), 140 mg, 0.63 mmol) in 2N HCl (2 mL) were added MeOH (2 mL) followed by NaNO2 (88 mg, 1.26 mmol) in portions at −10° C. After the mixture was warmed up to 0° C., H2O (3 mL) was added to the above mixture and the mixture was stirred at 95° C. for 1 h. 0.1N HCl (30 mL) was added and the mixture was extracted with ethyl acetate (50 mL) three times. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give 130 mg of the title compound: 1H NMR (CD3OD, 500 MHz) δ ppm 2.19 (2H, m), 2.62 (2H, m), 3.94 (2H, m), 7.27 (1H, m), 7.47 (1H, m), 7.66 (1H, m). MS (ESI) (M−H)− 220.12.

후처리

  1. extractionthe mixture was extracted with ethyl acetate (50 mL) three times
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-00466c6dd8b2492ea5d9b03de649f6cd
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07981913B2

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