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

HRID 882573Notes

Reaction equation

HRID 882573 reaction equation
[CH3:1][O:2][C@@H:3]([C@@H:12]([NH:17][CH3:18])[C@@H:13]([CH3:16])[CH2:14][CH3:15])[CH2:4][C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[CH2:19]([O:26][C:27]([NH:29][C@H:30]([C:34]([OH:36])=O)[CH:31]([CH3:33])[CH3:32])=[O:28])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.F[B-](F)(F)F.BrC1C=CC=C[N+]=1CC.C(N(CC)C(C)C)(C)C.[Cl-].[Na+]>ClCCl>[CH2:19]([O:26][C:27]([NH:29][C@H:30]([C:34]([N:17]([CH3:18])[C@@H:12]([C@@H:13]([CH3:16])[CH2:14][CH3:15])[C@H:3]([O:2][CH3:1])[CH2:4][C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6])=[O:36])[CH:31]([CH3:32])[CH3:33])=[O:28])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

7

Reactant 5

HCID 5234Sodium ChlorideHCID 81531DiisopropylethylamineHCID 726987N-Carbobenzoxy-L-valineHCID 27363002-Bromo-1-ethylpyridinium tetrafluoroborateHCID 10061126(3R,4S,5S)-tert-Butyl 3-methoxy-5-methyl-4-(methylamino)heptanoate2×

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 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-10 °C

Procedure

10.65 g (41.058 mmol) of tert-butyl (3R,4S,5S)-3-methoxy-5-methyl-4-(methylamino)heptanoate (starting compound 2b) were taken up in 250 ml of dichloromethane and the solution was cooled to −10° C. Then, while stirring, 10.317 g (41.058 mmol) of N-[(benzyloxy)carbonyl]-L-valine, 16.866 g (61.586 mmol) of 2-bromo-1-ethylpyridinium tetrafluoroborate (BEP) and 28.6 ml of N,N-diisopropylethylamine were added, and the mixture was subsequently stirred at RT for 20 h. The reaction mixture was then diluted with dichloromethane and shaken twice with saturated sodium chloride solution, dried over sodium sulphate, filtered and concentrated. The residue was purified by flash chromatography on silica gel with 4:1 petroleum ether/ethyl acetate as the eluent. The corresponding fractions were concentrated and the residue was dried under high vacuum overnight. 10.22 g (51% of theory) of the title compound were obtained as a yellowish oil.

Workup

  1. stirringthe mixture was subsequently stirred at RT for 20 h
  2. dry with materialdried over sodium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography on silica gel with 4:1 petroleum ether/ethyl acetate as the eluent
  6. concentrationThe corresponding fractions were concentrated
  7. customthe residue was dried under high vacuum overnight

Sources & evidence

ORD record
ord-381e6cad54c448459e86e5ad76d43551
Source dataset
uspto-grants-2015_03
Patent number
US08992932B2

Reaction notes

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