Ammonium Chloride → tert-butyl (3S,5S,8S)-8-(benzyloxymethyl)-6-hydroxy-3-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-2,9-dimethyldecan-5-ylcarbamate

HRID 660395ノート

反応式

HRID 660395 の反応式
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([CH2:15][C@H:16]([CH:29]([CH3:31])[CH3:30])[CH2:17][C@H:18]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:19]=[O:20])[CH:13]=2)[CH:8]=[N:7]1.[CH2:32]([O:39][CH2:40][C@H:41]([CH:45]([CH3:47])[CH3:46])[CH2:42][Mg]Br)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[NH4+].[Cl-]>C1COCC1>[CH2:32]([O:39][CH2:40][C@H:41]([CH:45]([CH3:47])[CH3:46])[CH2:42][CH:19]([OH:20])[C@@H:18]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:26])([CH3:25])[CH3:27])[CH2:17][C@H:16]([CH2:15][C:12]1[CH:13]=[C:14]2[C:9]([CH:8]=[N:7][N:6]2[CH2:5][CH2:4][CH2:3][O:2][CH3:1])=[CH:10][CH:11]=1)[CH:29]([CH3:31])[CH3:30])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

参加物

5

反応物 3

HCID 25517Ammonium ChlorideHCID 59630972tert-butyl (2S,4S)-4-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-5-methyl-1-oxohexan-2-ylcarbamateHCID 178448287HCID 178448287、化合物

生成物 1

HCID 59630979tert-butyl (3S,5S,8S)-8-(benzyloxymethyl)-6-hydroxy-3-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-2,9-dimethyldecan-5-ylcarbamate収率 33%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

A 250-mL, three-neck, round-bottom flask equipped with a condenser under N2 was charged with Mg powder (1.36 g, 56.7 mmol). The mixture was warmed briefly with a heat gun and a solution (S)-((2-(bromomethyl)-3-methylbutoxy)methyl)benzene (10.5 g, 37.8 mmol) in anhydrous THF (100 mL) was added dropwise. When the reaction mixture reached reflux temperature the heat gun was stopped. The mixture was stirred for an additional 30 min to afford a solution of (S)-(2-(benzyloxymethyl)-3-methylbutyl)magnesium bromide. A second 250-mL, three-neck round-bottom flask was charged with a solution of tert-butyl (2S,4S)-4-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-5-methyl-1-oxohexan-2-ylcarbamate (2.7 g, 6.3 mmol) in anhydrous THF (50 mL) and cooled to −78° C. under N2 and the solution was stirred for 30 min. The freshly prepared solution of (S)-(2-(benzyloxymethyl)-3-methylbutyl)magnesium bromide prepared above was added dropwise and the mixture was warmed to rt and stirred overnight. 10% aq NH4Cl was added and the mixture was extracted with EtOAc (3×50 mL). The combined organic layers were washed brine, dried and evaporated. The residue was purified by flash chromatography on silica gel to afford the crude tert-butyl (3S,5S,8S)-8-(benzyloxymethyl)-6-hydroxy-3-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-2,9-dimethyldecan-5-ylcarbamate (1.3 g, 33% yield) as an 11:5 mixture of diastereomers at the alcohol center.

後処理

  1. additionabove was added dropwise
  2. temperaturethe mixture was warmed to rt
  3. stirringstirred overnight
  4. extractionthe mixture was extracted with EtOAc (3×50 mL)
  5. washThe combined organic layers were washed brine
  6. customdried
  7. customevaporated
  8. customThe residue was purified by flash chromatography on silica gel

出典と根拠

ORDレコード
ord-62c60e4cf5a341aca664d4282019e222
出典データセット
uspto-grants-2011_12
特許番号
US08084485B2

反応ノート

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