Diisopropylamine → methyl 3-[1-(2-(1-adamantyl)ethyl)2-n-butyl-1H-imidazol-5-yl]-3-hydroxy-2-(2-thienylmethyl)propanoate

HRID 2081858Notes

Reaction equation

HRID 2081858 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[S:13]1[CH:17]=[CH:16][CH:15]=[C:14]1[CH:18]=[CH:19][C:20]([O:22][CH3:23])=[O:21].[C:24]12([CH2:34][CH2:35][N:36]3[C:40]([CH:41]=[O:42])=[CH:39][N:38]=[C:37]3[CH2:43][CH2:44][CH2:45][CH3:46])[CH2:33][CH:28]3[CH2:29][CH:30]([CH2:32][CH:26]([CH2:27]3)[CH2:25]1)[CH2:31]2.[Cl-].[NH4+]>CCCCCC.O1CCCC1.O>[C:24]12([CH2:34][CH2:35][N:36]3[C:40]([CH:41]([OH:42])[CH:19]([CH2:18][C:14]4[S:13][CH:17]=[CH:16][CH:15]=4)[C:20]([O:22][CH3:23])=[O:21])=[CH:39][N:38]=[C:37]3[CH2:43][CH2:44][CH2:45][CH3:46])[CH2:33][CH:28]3[CH2:29][CH:30]([CH2:32][CH:26]([CH2:27]3)[CH2:25]1)[CH2:31]2

Participants

9

Reactant 5

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 2778970Methyl 3-(thiophen-2-yl)acrylateHCID 199369031-[2-(1-Adamantyl)ethyl]-2-n-butyl-imidazol-5-carboxaldehydeHCID 178418339Butyllithium

Product 1

HCID 19936767methyl 3-[1-(2-(1-adamantyl)ethyl)2-n-butyl-1H-imidazol-5-yl]-3-hydroxy-2-(2-thienylmethyl)propanoate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Procedure

Diisopropylamine (0.563 g) was covered with 5 ml of tetrahydrofuran and 2 ml of 2.5M n-butyl lithium in hexane was added at -78° C. The mixture was stirred for 15 minutes, was then methyl 3-(2-thienyl)propenoate (0.89 g) in 3 ml of tetrahydrofuran was added. After 20 minutes, 1.04 g of 1-[2-(1-adamantyl)ethyl]-2-n-butyl-imidazol-5-carbox-aldehyde in 3 ml of tetrahydrofuran was added and the mixture was stirred for 30 minutes at -78° C. The mixture was poured into 40 ml of saturated ammonium chloride in water, extracted with ether, dried over magnesium sulfate, filtered, concentrated and chromatographed on silica gel eluting with 70% ethyl acetate and 30% hexane to give methyl 3-[1-(2-(1-adamantyl)ethyl)-2-n-butyl-1H -imidazol-5-yl]-3-hydroxy-2-(2-thienylmethyl)propanoate. To 1.27 g of this compound in methylene chloride (25 ml) was added 4-dimethylaminopyridine (1.25 g), then acetic anhydride (2.75 g) was added dropwise. The mixture was stirred for one hour, then poured into water and worked up to give 3-acetoxy-3-[1-(2-(1-adamantyl)ethyl)-2-n-butyl-1H -imidazol-5-yl]-2-(2-thienylmethyl)propanoate.

Workup

  1. additionwas added at -78° C
  2. waitAfter 20 minutes
  3. stirringthe mixture was stirred for 30 minutes at -78° C
  4. extractionextracted with ether
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customchromatographed on silica gel eluting with 70% ethyl acetate and 30% hexane

Sources & evidence

ORD record
ord-36fb26294ab749638289aa62c01aca0e
Source dataset
uspto-grants-1993_02
Patent number
US05185351

Reaction notes

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