Sodium triacetoxyborohydride → 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(3,3-dimethylmorpholino)butan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

HRID 932161노트

반응식

HRID 932161 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:24][CH3:25])[CH:22]=O)[C:11](=[O:26])[C@:10]([CH2:28][C:29]([OH:31])=[O:30])([CH3:27])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.Cl.[CH3:33][C:34]1([CH3:40])[CH2:39][O:38][CH2:37][CH2:36][NH:35]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.[NH4+].[Cl-]>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)[N:12]([C@@H:21]([CH2:24][CH3:25])[CH2:22][N:35]3[CH2:36][CH2:37][O:38][CH2:39][C:34]3([CH3:40])[CH3:33])[C:11](=[O:26])[C@:10]([CH2:28][C:29]([OH:31])=[O:30])([CH3:27])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

참가 물질

6

반응물 3

HCID 5049666Sodium triacetoxyborohydrideHCID 223428633,3-Dimethylmorpholine hydrochlorideHCID 585738802-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-1-oxobutan-2-yl)piperidin-3-yl)acetic acid

생성물 1

HCID 585738742-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(3,3-dimethylmorpholino)butan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 25517Ammonium Chloride용매

실험 절차

To a solution of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-1-oxobutan-2-yl)piperidin-3-yl)acetic acid (70 mg, 0.151 mmol; Example 210, Step A) in DCE (3 mL) was added 45.9 mg (0.303 mmol) of 3,3-dimethylmorpholine hydrochloride (Cottle, D.; Jeltsch, A.; Stoudt, T.; Walters, D. Journal of Organic Chemistry. 1946, 11(3), 286-91; Note: reference is for the free base) and sodium triacetoxyborohydride (64.2 mg, 0.303 mmol). After stirring overnight, the mixture was diluted with sat. aq. NH4Cl solution. The mixture was extracted with DCM (2×). The combined organic layers were washed with sat. aq. NaCl solution, dried over anhydrous Na2SO4, filtered and the filtrate was concentrated. The residue was purified by preparative thin layer chromatography on silica gel (eluent: 50% ethyl acetate/hexanes). The product containing fractions were pooled, concentrated and repurified by preparative thin layer chromatography on silica gel (eluent: 10% MeOH/DCM) to afford the title compound.

후처리

  1. extractionThe mixture was extracted with DCM (2×)
  2. washThe combined organic layers were washed with sat. aq. NaCl solution
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. customThe residue was purified by preparative thin layer chromatography on silica gel (eluent: 50% ethyl acetate/hexanes)
  7. additionThe product containing fractions
  8. concentrationconcentrated
  9. customrepurified by preparative thin layer chromatography on silica gel (eluent: 10% MeOH/DCM)

출처 및 근거

ORD 기록
ord-eea310d4c18a4683b1f9c3331912876e
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09296736B2

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