Benzyl Bromide → (2S)-2-(((9H-fluoren-9-ylmethoxy)carbonyl)amino)-4-hydroxybutanoic acid

HRID 2424257

反応式

HRID 2424257 の反応式
CC([O:5][C:6]([C@@H:8]([NH:13][C:14]([O:16][CH2:17][CH:18]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]2[C:19]1=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:15])[CH2:9][C:10](O)=[O:11])=[O:7])(C)C.C(N(CC)CC)C.C(OC(Cl)=O)C(C)C.[BH4-].[Na+].[H-].[Na+].C(Br)C1C=CC=CC=1>O1CCCC1.O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:14]([NH:13][C@H:8]([C:6]([OH:7])=[O:5])[CH2:9][CH2:10][OH:11])([O:16][CH2:17][CH:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:25]2[C:30]1=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:15]

参加物

10

反応物 6

HCID 7498Benzyl BromideHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 7017910(S)-3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanoic acid

生成物 1

HCID 15449971(2S)-2-(((9H-fluoren-9-ylmethoxy)carbonyl)amino)-4-hydroxybutanoic acid

試薬・触媒・溶媒 3

HCID 67553Tetrabutylammonium Iodide触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 10.0 mmol of Fmoc Asp-OtBu (42) in 50 mL of dry tetrahydrofuran, kept at −20° C. under nitrogen, is added 1.77 mL (12.7 mmol) of triethyl amine, followed by the slow addition of 1.57 mL (12.0 mmol) of isobutylchloroformate. The mixture is stirred for 30 minutes, and then poured slowly over an ice-cold solution of 3.77 g (99.6 m mol) of sodium borohydride in 10 mL of water, keeping the temperature below 5° C. The reaction is stirred at 0° C. for 15 minutes, and then quenched with 1N hydrochloric acid solution. The reaction mixture is diluted with 100 mL of ethyl acetate, and the layers separated. The organic layer was washed with 2×25 mL of 1N hydrochloric acid solution, 2×25 mL of water, dried over magnesium sulfate and concentrated, and purified by silica gel column chromatography. Purified compound is then dissolved in 30 mL of tetrahydrofuran, and 12 mmol of 60% sodium hydride dispersion in mineral oil is added, followed by 0.2 mmol of tetrabutylammonium iodide and 12 mmol of benzyl bromide, and the mixture is stirred overnight, quenched with 50 mL of saturated aqueous sodium bicarbonate, and extracted with 100 mL of ethyl acetate. The compound is then purified by silica gel column chromatography.

後処理

  1. customkept at −20° C. under nitrogen
  2. customthe temperature below 5° C
  3. stirringThe reaction is stirred at 0° C. for 15 minutes
  4. customquenched with 1N hydrochloric acid solution
  5. additionThe reaction mixture is diluted with 100 mL of ethyl acetate
  6. customthe layers separated
  7. washThe organic layer was washed with 2×25 mL of 1N hydrochloric acid solution, 2×25 mL of water
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. custompurified by silica gel column chromatography
  11. dissolutionPurified compound is then dissolved in 30 mL of tetrahydrofuran
  12. stirringthe mixture is stirred overnight
  13. customquenched with 50 mL of saturated aqueous sodium bicarbonate
  14. extractionextracted with 100 mL of ethyl acetate
  15. customThe compound is then purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-9fc3ec3651204b569698228d62bf205f
出典データセット
uspto-grants-2011_06
特許番号
US07964181B2

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