Butyryl chloride → HCID 9831299, compound

HRID 1291793Notes

Reaction equation

HRID 1291793 reaction equation
[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]

Participants

7

Reactant 2

HCID 8855Butyryl chloride3×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×

Product 1

HCID 9831299HCID 9831299, compound

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-49a7c985d1b1438d81253e47454f8ead
Source dataset
uspto-grants-1998_05
Patent number
US05753652

Reaction notes

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