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

反応式

HRID 1014874 の反応式
[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]

参加物

8

反応物 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

生成物 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

試薬・触媒・溶媒 3

HCID 313Hydrochloric Acid溶媒2 回HCID 887Methanol溶媒HCID 962Water溶媒

反応条件

温度
0 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-00466c6dd8b2492ea5d9b03de649f6cd
出典データセット
uspto-grants-2011_07
特許番号
US07981913B2

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