Butyryl chloride → HCID 9831299、化合物

HRID 1291793ノート

反応式

HRID 1291793 の反応式
[C:1](Cl)(=[O:5])[CH2:2][CH2:3][CH3:4].[OH:7][C@H:8]([C@@H:30]([NH:38][C:39](=[O:49])[C@H:40]([CH:46]([CH3:48])[CH3:47])[NH:41][C:42]([O:44][CH3:45])=[O:43])[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:9][N:10]([CH2:23][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)[NH:11][C:12](=[O:22])[C@H:13]([CH:19]([CH3:21])[CH3:20])[NH:14][C:15]([O:17][CH3:18])=[O:16]>CN(C1C=CN=CC=1)C.O1CCOCC1.N1C=CC=CC=1.C(OCC)(=O)C>[C:1]([O:7][C@H:8]([C@@H:30]([NH:38][C:39](=[O:49])[C@H:40]([CH:46]([CH3:48])[CH3:47])[NH:41][C:42]([O:44][CH3:45])=[O:43])[CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[CH2:9][N:10]([CH2:23][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)[NH:11][C:12](=[O:22])[C@H:13]([CH:19]([CH3:20])[CH3:21])[NH:14][C:15]([O:17][CH3:18])=[O:16])(=[O:5])[CH2:2][CH2:3][CH3:4]

参加物

7

反応物 2

HCID 8855Butyryl chloride3 回HCID 461993methyl N-[(1S)-1-[[(1S,2S)-1-benzyl-3-[cyclohexylmethyl-[[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]amino]amino]-2-hydroxy-propyl]carbamoyl]-2-methyl-propyl]carbamate2 回

生成物 1

HCID 9831299HCID 9831299、化合物

試薬・触媒・溶媒 4

HCID 142844-(Dimethylamino)pyridine触媒2 回HCID 1049Pyridine溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

50 μ(0.495 mmol) of butyric acid chloride and 2 mg (0.017 mmol) of DMAP are added to an ice-cooled mixture of 200 mg (0.33 mmol) of 1-[2(S)-hydroxy-3(S)-(N-(methoxy-carbonyl)-(L)-valyl)amino-4-phenyl-butyl]-1-[cyclohexylmethyl]-2-[N-methoxycarbonyl-(L)-valyl]-hydrazine (Example 73a) in 2.6 ml of dioxane and 0.4 ml of pyridine. After 18 h at RT, according to HPLC there is still 1-[2(S)-hydroxy-3(S)-(N-(methoxycarbonyl)-(L)-valyl)amino-4-phenyl-butyl]-1-[cyclohexylmethyl]-2-[N-methoxycarbonyl-(L)-valyl]-hydrazine present in the reaction mixture, and therefore a further 0.75 equivalents of butyric acid chloride and a few granules of DMAP are added. After a further 18 h, a 3rd portion of 1.5 equivalents of butyric acid chloride is added and the mixture is further stirred for one night at RT (→HPLC: fully reacted). The reaction mixture is diluted with ethyl acetate and washed with 2 portions of saturated NaHCO3 solution, water and brine, the aqueous phases are extracted twice with ethyl acetate, and the organic phases are dried with Na2SO4 and concentrated by evaporation. Digestion of the oily residue from hexane in an ultrasound bath yields the pure title compound: TLC Rf (O)=0.67; tRet (V)=17.2 min; FAB-MS (M+H)+ =676.

後処理

  1. temperaturecooled
  2. waitAfter a further 18 h
  3. customfully reacted)
  4. washwashed with 2 portions of saturated NaHCO3 solution, water and brine
  5. extractionthe aqueous phases are extracted twice with ethyl acetate
  6. dry with materialthe organic phases are dried with Na2SO4
  7. concentrationconcentrated by evaporation

出典と根拠

ORDレコード
ord-49a7c985d1b1438d81253e47454f8ead
出典データセット
uspto-grants-1998_05
特許番号
US05753652

反応ノート

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