Acetic Acid → (3S)tetrahydro-3-furanyl N-((1S,2R)-1-benzyl-3-(cyclohexyloxy)[(4-methoxyphenyl) sulfonyl]amino-2-hydroxypropyl)carbamate

HRID 29178

반응식

HRID 29178 반응식
[CH2:1]([C@H:8]([NH:31][C:32](=[O:38])[O:33][C:34](C)([CH3:36])[CH3:35])[C@@H:9]([OH:30])[CH:10]([NH:18][S:19]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=1)(=[O:21])=[O:20])[O:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:39](=O)(O[C@H]1CCOC1)[O:40]N1C(=O)CCC1=O.C(O)(=O)C>C(Cl)Cl.C(O)(C(F)(F)F)=O>[CH2:1]([C@H:8]([NH:31][C:32](=[O:38])[O:33][C@H:34]1[CH2:36][CH2:39][O:40][CH2:35]1)[C@@H:9]([OH:30])[CH:10]([NH:18][S:19]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=1)(=[O:21])=[O:20])[O:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

5

반응물 3

HCID 176Acetic AcidHCID 11229944Carbonic Acid 2,5-Dioxopyrrolidin-1-yl (S)-Tetrahydrofuran-3-yl EsterHCID 69223512tert-butyl N-((1S,2R)-1-benzyl-3-(cyclohexyloxy)((4-methoxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate

생성물 1

HCID 69220929(3S)tetrahydro-3-furanyl N-((1S,2R)-1-benzyl-3-(cyclohexyloxy)[(4-methoxyphenyl) sulfonyl]amino-2-hydroxypropyl)carbamate수율 67.5%

시약·촉매·용매 1

HCID 21863450Trifluoroacetic acid methylene chloride용매

실험 절차

tert-butyl N-((1S,2R)-1-benzyl-3-(cyclohexyloxy)[(4-methoxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate (0.09 mmol, 50 mg) was dissolved in a 1:1 solution of CH2Cl2/TFA (1 mL) and allowed to stir at room temperature for 1 hour. The solution was then extracted into ethyl acetate, washed with saturated sodium bicarbonate solution and brine, dried over magnesium sulfate, and concentrated to a clear oil. The resulting oil was then dissolved in THF (1 mL) and combined with 2,5-dioxo-1-pyrrolidinyl [(3S)tetrahydro-3-furanyl] carbonate (0.05 mmol, 13 mg) DIEA (0.08 mmol, 14 μL) and allowed to stir for 15 hours. The reaction was neutralized by the addition of acetic acid and partitioned between water and ethyl acetate. The organic layer was washed with saturated sodium bicarbonate and brine, and dried over magnesium sulfate. The crude product was concentrated to a white solid and purified by silica gel chromatography (1:1 hexanes/ethyl acetate), providing 19 mg (37%) of a white solid. H1-NMR (CDCl3): δ 7.70 (2H,d), 7.29-7.17 (6H,m), 6.97 (2H,d), 5.1 (1H,s), 4.76 (1H,d), 4.17 (1H,m), 3.86 (3H,s), 3.87-3.70 (6H,m), 3.68-3.60 (1H,m), 3.06 (1H,bs), 2.89 (2H,m), 2.02 (3H,m), 1.89 (1H,m), 1.71 (2H,m), 1.28-1.08 (6H,m); MS (ESI): M+Na=585.

후처리

  1. extractionThe solution was then extracted into ethyl acetate
  2. washwashed with saturated sodium bicarbonate solution and brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated to a clear oil
  5. dissolutionThe resulting oil was then dissolved in THF (1 mL)
  6. stirringto stir for 15 hours
  7. custompartitioned between water and ethyl acetate
  8. washThe organic layer was washed with saturated sodium bicarbonate and brine
  9. dry with materialdried over magnesium sulfate
  10. concentrationThe crude product was concentrated to a white solid
  11. custompurified by silica gel chromatography (1:1 hexanes/ethyl acetate)

출처 및 근거

ORD 기록
ord-1dc3b8bb42824473b393fed260e10db4
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07419967B2

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