Ammonium Chloride → (3R,4S,5S)-tert-butyl 4-((S)-2-(((benzyloxy)carbonyl)amino)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoate

HRID 1022515Notes

Reaction equation

HRID 1022515 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:16]([OH:18])=O)[CH:13]([CH3:15])[CH3:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:20][O:21][C@@H:22]([C@@H:31]([NH:36][CH3:37])[C@@H:32]([CH3:35])[CH2:33][CH3:34])[CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[Cl-].[NH4+]>CN(C=O)C.C(OCC)(=O)C>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:16]([N:36]([CH3:37])[C@@H:31]([C@@H:32]([CH3:35])[CH2:33][CH3:34])[C@H:22]([O:21][CH3:20])[CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[O:18])[CH:13]([CH3:14])[CH3:15])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 6

HCID 25517Ammonium ChlorideHCID 81531Diisopropylethylamine2×HCID 726987N-Carbobenzoxy-L-valine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 27960291-Hydroxybenzotriazole hydrate2×HCID 14730240(3r,4s,5s)-Tert-butyl 3-methoxy-5-methyl-4-(methylamino)heptanoate hydrochloride2×

Product 1

HCID 10529182(3R,4S,5S)-tert-butyl 4-((S)-2-(((benzyloxy)carbonyl)amino)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

425 mg (1.7 mmol) of N-[(benzyloxy)carbonyl]-L-valine were dissolved in 50 ml of DMF, and 500 mg (1.7 mmol) of tert-butyl (3R,4S,5S)-3-methoxy-5-methyl-4-(methylamino)heptanoate hydrochloride (Starting Material 2), 356 mg (1.9 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 285 mg (1.9 mmol) of 1-hydroxy-1H-benzotriazole hydrate and 655 mg (5.1 mmol) of N,N-diisopropylethylamine were added in succession. The mixture was stirred at RT for 20 h. Another 142 mg (0.5 mmol) of N-[(benzyloxy)carbonyl]-L-valine, 119 mg (0.6 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 95 mg (0.6 mmol) of 1-hydroxy-1H-benzotriazole hydrate and 218 mg (1.7 mmol) of N,N-diisopropylethylamine were added, and the mixture was treated with ultrasound for 90 min. The mixture was then poured into a mixture of semisaturated aqueous ammonium chloride solution and ethyl acetate. The organic phase was separated off, washed successively with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over magnesium sulphate, filtered and concentrated. The residue was purified by preparative HPLC. This gave 329 mg (40% of theory) of the title compound as a colourless oil.

Workup

  1. additionthe mixture was treated with ultrasound for 90 min
  2. customThe organic phase was separated off
  3. washwashed successively with saturated sodium bicarbonate solution and saturated sodium chloride solution
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-ab0af39e7b6a4638afeed1e3fab42e68
Source dataset
uspto-grants-2014_05
Patent number
US08722629B2

Reaction notes

Loading…