Lithium borohydride → Boc-His(Ts) 3-cyclohexyl-alaninol

HRID 1614058Notes

Reaction equation

HRID 1614058 reaction equation
[NH:1]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@H:2]([C:19]([OH:21])=[O:20])[CH2:3][C:4]1[N:8]=[CH:7][N:6]([S:9]([C:12]2[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=2)(=[O:11])=[O:10])[CH:5]=1.C[O:30][C:31](=O)[C@H:32]([CH2:34][CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1)[NH2:33].[BH4-].[Li+]>C1COCC1.C(O)C>[NH:1]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@H:2]([C:19]([OH:21])=[O:20])[CH2:3][C:4]1[N:8]=[CH:7][N:6]([S:9]([C:12]2[CH:13]=[CH:14][C:15]([CH3:16])=[CH:17][CH:18]=2)(=[O:11])=[O:10])[CH:5]=1.[CH:35]1([CH2:34][C@@H:32]([CH2:31][OH:30])[NH2:33])[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1

Participants

5

Reactant 2

HCID 4148881Lithium borohydrideHCID 131717822Boc-His(Ts) 3-cyclohexylalanine methyl ester

Product 1

HCID 131717821Boc-His(Ts) 3-cyclohexyl-alaninolYield 72%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

The extract is dried over MgSO4 and evaporated to dryness in vacuo to quantitatively obtain 3-cyclohexylalanine methyl ester [16a] as an oil. The product is then, without further purification, dissolved in dichloromethane (50 ml) To the solution are added Boc-His(Ts)·DCHA [8a] (10.7 g, 18.11 mmol, 1.3 eq) and diethyl cyanophosphonate (2.95 g, 18.1 mmol, 1.3 eq), and the mixture is stirred for 1.5 hours at room temperature. The reaction mixture is subjected to silica gel chromatography (SiO2 :300 g, CH2Cl2 :MeOH=99:1) to give a purified Boc-His(Ts)-3-cyclohexylalanine methyl ester [17a] (7.43 g, 93%) as an oil. To a solution of the dipeptide ester [17a] (3.0 g, 5.2 mmol) in THF (6 ml) and ethanol (6 ml) is added a 2N solution of lithium borohydride in THF (3 ml, 6 mmol) with stirring and ice-cooling. After 20 minutes stirring, the mixture is allowed to react at room temperature for additional one hour. The solvent is removed in vacuo and the residue added ice water and saturated aqueous ammonium chloride is extracted with dichloromethane (20 ml×3). The organic layer is washed with saturated aqueous sodium chloride, dried over MgSO4, evaporated to dryness in vacuo and the residue is purified by silica gel chromatography (SiO2 : 200 g, CH2Cl2 :MeOH=98:2) to obtain Boc-His(Ts)-3-cyclohexyl-alaninol [18a] (2.06 g, 72%) as an oil.

Workup

  1. temperatureice-cooling
  2. stirringAfter 20 minutes stirring
  3. customto react at room temperature for additional one hour
  4. customThe solvent is removed in vacuo
  5. additionthe residue added ice water and saturated aqueous ammonium chloride
  6. extractionis extracted with dichloromethane (20 ml×3)
  7. washThe organic layer is washed with saturated aqueous sodium chloride
  8. dry with materialdried over MgSO4
  9. customevaporated to dryness in vacuo
  10. customthe residue is purified by silica gel chromatography (SiO2 : 200 g, CH2Cl2 :MeOH=98:2)

Sources & evidence

ORD record
ord-cfd99e7370eb47ee9f760be37f6c4776
Source dataset
uspto-grants-1993_03
Patent number
US05194608

Reaction notes

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