Hydrochloric Acid → n-(1-(n-hydroxycarbamoyl)(1S)-3-phenylpropyl)(tert-butoxy)-carboxamide

HRID 532096

反応式

HRID 532096 の反応式
[CH3:1][C:2]([O:5][C:6]([NH:8][C@H:9]([C:18]([OH:20])=O)[CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:7])([CH3:4])[CH3:3].C[Si](C=[N+]=[N-])(C)C.[NH2:28][OH:29].Cl.[OH-].[K+].Cl>CCOCC.CO.C(Cl)Cl.CO>[OH:29][NH:28][C:18]([C@@H:9]([NH:8][C:6]([O:5][C:2]([CH3:4])([CH3:3])[CH3:1])=[O:7])[CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:20]

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 167693TrimethylsilyldiazomethaneHCID 443297Hydroxyamine hydrochlorideHCID 7018726(2S)-2-(((tert-butoxy)carbonyl)amino)-4-phenylbutanoic acid

生成物 1

HCID 44194191n-(1-(n-hydroxycarbamoyl)(1S)-3-phenylpropyl)(tert-butoxy)-carboxamide収率 49.9%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 3283Diethyl Ether溶媒HCID 21226129Dichloromethane methanol溶媒

反応条件

温度
0 °C

実験手順

A solution of crude Boc-Hfe-OH (10.0 mmol theoretical) in 4:1 CH2Cl2/MeOH (50.0 mL) was treated with (trimethylsilyl)diazomethane (12.0 mmol; 6.00 mL of a 2.0 M solution in Et2O) dropwise over 0.25 h at 22° C. CAUTION: vigorous gas evolution. The resulting yellow solution was stirred an additional 0.25 h to ensure complete methylation. Excess (trimethylsilyl)diazomethane was consumed by the dropwise addition of glacial AcOH, then all volatiles removed in vacuo. The crude ester was redissolved in MeOH (50.0 mL), cooled to 0° C. and treated with a previously prepared suspension of H2NOH.HCl (2.08 g, 30.0 mmol) and KOH (3.37 g, 60.0 mmol) in MeOH (50.0 mL); a large bore cannula needle was required for the transfer. The resulting suspension then warmed slowly to 22° C. overnight as the ice bath melted. After 14 h, the suspension was acidified with conc. HCl to pH 4-5 then all volatiles removed in vacuo. The solids were triturated with several portions of hot EtOAc (5×10 mL) and removed by filtration through a scintered glass funnel of medium porosity. The combined filtrates were collected and concentrated in vacuo to an off-white powder. Purification through recrystallization from hot EtOAc (200 mL) afforded a white microcrystalline solid (1.47 g, 4.99 mmol, 49.9%). The spectral data obtained for this material are in accord with that described for the product of Part 1A.

後処理

  1. customExcess (trimethylsilyl)diazomethane was consumed by the dropwise addition of glacial AcOH
  2. customall volatiles removed in vacuo
  3. dissolutionThe crude ester was redissolved in MeOH (50.0 mL)
  4. waitAfter 14 h
  5. customall volatiles removed in vacuo
  6. customThe solids were triturated with several portions of hot EtOAc (5×10 mL)
  7. customremoved by filtration through a scintered glass funnel of medium porosity
  8. customThe combined filtrates were collected
  9. concentrationconcentrated in vacuo to an off-white powder
  10. customPurification
  11. customthrough recrystallization from hot EtOAc (200 mL)

出典と根拠

ORDレコード
ord-11641652156f485d9bfa8015397c3e76
出典データセット
uspto-grants-2014_10
特許番号
US08852553B2

関連ノート

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