Methanol → N2 [(1,1-Dimethylethoxy)carbonyl]-N6-[(phenylmethoxy)carbonyl]-L-lysine, methyl ester

HRID 745340Notes

Reaction equation

HRID 745340 reaction equation
[C:1](=O)([O-])[O-].[Cs+].[Cs+].[N:7]#[N:8].[CH3:9][C:10]([CH3:35])([O:12][C:13]([NH:15][C@H:16]([C:32]([OH:34])=[O:33])[CH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23])=[O:14])[CH3:11].CO.CI>C(OCC)(=O)C>[N:7]#[N:8].[CH3:11][C:10]([CH3:35])([O:12][C:13]([NH:15][C@H:16]([C:32]([O:34][CH3:1])=[O:33])[CH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:22]([O:24][CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)=[O:23])=[O:14])[CH3:9]

Participants

6

Reactant 4

HCID 887Methanol2×HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 86742311N2 [(1,1-dimethylethoxy)carbonyl]-N6-[(phenylmethoxy)carbonyl]-L-lysine

Product 1

HCID 131714291N2 [(1,1-Dimethylethoxy)carbonyl]-N6-[(phenylmethoxy)carbonyl]-L-lysine, methyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Cesium carbonate (2.14 g., 6.55 mmole) is added to a mixture of N2 -[(1,1-dimethylethoxy)carbonyl]-N6 -[(phenylmethoxy)carbonyl]-L-lysine (5.0 g., 13.10 mmole) and 20% aqueous methanol (30 ml.). The solution becomes homogeneous after 5 minutes, the methanol is stripped, and the residual water is removed azetropically with acetonitrile (twice). The resulting oil is taken up in dry methylene chloride (10 ml.) and treated with methyl iodide (1.6 ml., 2.0 eq.) at 25° in an argon atmosphere. After 4 hours the reaction mixture is taken up in ethyl acetate and washed successively with water, saturated sodium bicarbonate and brine, dried (MgSO4), and evaporated. The residue (4.7 g.) is chromatographed on silica (160 g.) eluting with hexane/ethyl acetate (3:1) to give 4.0 g. of N2 -[(1,1-dimethylethoxy)carbonyl]-N6 -[(phenylmethoxy)carbonyl]-L-lysine, methyl ester as an oil after evaporation. TLC (hexane/ethyl acetate; 2:1) major spot at Rf =0.3.

Workup

  1. customthe residual water is removed azetropically with acetonitrile (twice)
  2. washwashed successively with water, saturated sodium bicarbonate and brine
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. customThe residue (4.7 g.) is chromatographed on silica (160 g.)
  6. washeluting with hexane/ethyl acetate (3:1)
  7. customto give 4.0 g
  8. customof N2 -[(1,1-dimethylethoxy)carbonyl]-N6 -[(phenylmethoxy)carbonyl]-L-lysine, methyl ester as an oil after evaporation

Sources & evidence

ORD record
ord-315314aeda644a579ef8d44141229929
Source dataset
uspto-grants-1986_07
Patent number
US04598071

Reaction notes

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