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 1048475ノート

反応式

HRID 1048475 の反応式
[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

参加物

6

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 25517Ammonium Chloride溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-d4c27581f1214d2f817681af2af8f52e
出典データセット
uspto-grants-2013_10
特許番号
US08569341B2

反応ノート

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