Hydrochloric Acid → Di-tert-butyl (4R)-4-{[5-(benzyloxy)pyridin-2-yl]methyl}-N-(tert-butoxycarbonyl)-L-glutamate

HRID 591282ノート

反応式

HRID 591282 の反応式
[C:1]([NH:8][C@H:9]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:10][CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:36]([O:43][C:44]1[CH:45]=[CH:46][C:47]([CH2:50]Br)=[N:48][CH:49]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.Cl>O1CCCC1>[CH2:36]([O:43][C:44]1[CH:45]=[CH:46][C:47]([CH2:50][C@H:11]([C:12]([O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[O:13])[CH2:10][C@@H:9]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[NH:8][C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])=[N:48][CH:49]=1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 797999495-(Benzyloxy)-2-(bromomethyl)pyridineHCID 86647571Di-tert-butyl Boc-L-glutamate

生成物 1

HCID 70957109Di-tert-butyl (4R)-4-{[5-(benzyloxy)pyridin-2-yl]methyl}-N-(tert-butoxycarbonyl)-L-glutamate収率 73.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
-75 °C

実験手順

540 mg (1.50 mmol) of di-tert-butyl Boc-glutamate (prepared according to J. Peptide Res. 2001, 58, 338) were dissolved in 6 mL of tetrahydrofuran and cooled to −75° C. 3.45 mL (3.45 mmol) of a 1M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran were added dropwise and the mixture was stirred at −75° C. for another 60 minutes. 460 mg (1.65 mmol) of 5-(benzyloxy)-2-(bromomethyl)pyridine in 5 mL of tetrahydrofuran were then added dropwise, and after stirring 2 hours at −75° C., 3.45 mL of 2N aqueous hydrochloric acid were added, and after stirring another 30 minutes at −75° C., the cooling bath was removed and the mixture was allowed to warm up to room temperature. The mixture was partitioned between dichloromethane and aqueous sodium bicarbonate, and the organic layer was dried over magnesium sulfate and evaporated. The crude residue was purified by column chromatography on silica gel (ethyl acetate in hexane 0%→100%) to give 610 mg of the desired compound as yellowish oil (66% yield).

後処理

  1. stirringafter stirring 2 hours at −75° C.
  2. stirringafter stirring another 30 minutes at −75° C.
  3. customthe cooling bath was removed
  4. temperatureto warm up to room temperature
  5. customThe mixture was partitioned between dichloromethane and aqueous sodium bicarbonate
  6. dry with materialthe organic layer was dried over magnesium sulfate
  7. customevaporated
  8. customThe crude residue was purified by column chromatography on silica gel (ethyl acetate in hexane 0%→100%)

出典と根拠

ORDレコード
ord-b1699b109f90479ab077bf600c5e98db
出典データセット
uspto-grants-2016_01
特許番号
US09238631B2

反応ノート

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