Ethyl Acetate → (2R,4R)-5-biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxypentanoic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester

HRID 2045140노트

반응식

HRID 2045140 반응식
[C:1]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:9][C@@H:10]([OH:14])[C:11]([OH:13])=[O:12])=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:36][C:37]1[O:38][C:39](=[O:43])[O:40][C:41]=1[CH3:42].CCOC(C)=O>CN(C=O)C>[CH3:42][C:41]1[O:40][C:39](=[O:43])[O:38][C:37]=1[CH2:36][O:12][C:11](=[O:13])[C@H:10]([OH:14])[CH2:9][C@H:8]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:7][C:4]1[CH:3]=[CH:2][C:1]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[CH:6][CH:5]=1

참가 물질

6

반응물 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 98555184-(Chloromethyl)-5-methyl-1,3-dioxol-2-oneHCID 67969342(2R,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxypentanoic acid

생성물 1

HCID 67969703(2R,4R)-5-biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxypentanoic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
0 °C

실험 절차

(2R,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxypentanoic acid (500 mg, 1.0 mmol, 1.0 eq.) was dissolved in dry DMF (10.0 mL). The solution was cooled to 0° C. and dicesium carbonate (465 mg, 1.4 mmol, 1.1 eq.) was added. The mixture was stirred for 30 minutes and 4-chloromethyl-5-methyl-1,3-dioxol-2-one (212 mg, 1.4 mmol, 1.1 eq.) was added. The resulting mixture was stirred for an additional 1 hour at 0° C., then warmed to room temperature while stirring. The mixture was further stirred overnight. EtOAc (20 mL) was added, followed by washing with saturated aqueous NaCl (100 mL). The product was dried under vacuum and purified using reverse phase chromatography (10-70% MeCN/H2O; 0.05% TFA over 70 minutes) to yield (2R,4R)-5-biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxypentanoic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester. This material was dissolved in 4N HCL in dioxane and stirred for 2 hours at room temperature. The material was dried under vacuum then azeotroped with toluene to yield (2R,4R)-4-amino-5-biphenyl-4-yl-2-hydroxypentanoic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester, which was used in the next step without further purification.

후처리

  1. stirringThe resulting mixture was stirred for an additional 1 hour at 0° C.
  2. temperaturewarmed to room temperature
  3. stirringwhile stirring
  4. waitThe mixture was further stirred overnight
  5. washby washing with saturated aqueous NaCl (100 mL)
  6. customThe product was dried under vacuum
  7. custompurified
  8. customphase chromatography (10-70% MeCN/H2O; 0.05% TFA over 70 minutes)

출처 및 근거

ORD 기록
ord-ad112c6a90d948b7ae87c2d18b76cf38
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08586536B2

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