2,6-Lutidine → ethyl (4S)-4-{[(benzyloxy)carbonyl]amino}-3-{[tert-butyl(dimethyl)silyl]oxy}-5-methylhexanoate

HRID 906956Notes

Reaction equation

HRID 906956 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH:21]([CH3:23])[CH3:22])[CH:13]([OH:20])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C(C)=CC=CC=1C.[CH3:32][C:33]([Si:36](OS(C(F)(F)F)(=O)=O)([CH3:38])[CH3:37])([CH3:35])[CH3:34]>C1COCC1>[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH:21]([CH3:22])[CH3:23])[CH:13]([O:20][Si:36]([C:33]([CH3:35])([CH3:34])[CH3:32])([CH3:38])[CH3:37])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 67390171ethyl (4S)-4-{[(benzyloxy)carbonyl]amino}-3-hydroxy-5-methylhexanoate

Product 1

HCID 67390315ethyl (4S)-4-{[(benzyloxy)carbonyl]amino}-3-{[tert-butyl(dimethyl)silyl]oxy}-5-methylhexanoateYield 88.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Under an argon atmosphere, to a solution (228 mL) of ethyl (4S)-4-{[(benzyloxy)carbonyl]amino}-3-hydroxy-5-methylhexanoate (14.74 g) in dehydrated THF was added 2,6-lutidine (7.33 g) with stirring under ice-cooling, and tert-butyl dimethylsilyl trifluoromethanesulfonate (14.46 g) was added dropwise. The mixture was gradually warmed to room temperature and stirred for 1.5 hr. The reaction mixture was poured into ice water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=19/1→4/1) to give ethyl (4S)-4-{[(benzyloxy)carbonyl]amino}-3-{[tert-butyl(dimethyl)silyl]oxy}-5-methylhexanoate as colorless oil (yield: 17.7 g).

Workup

  1. temperaturecooling
  2. stirringstirred for 1.5 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=19/1→4/1)

Sources & evidence

ORD record
ord-c8b22f40baf244979c71ff8683c6421b
Source dataset
uspto-grants-2011_09
Patent number
US08013008B2

Reaction notes

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