Triethylamine → 3(S)-(3,4-dichlorophenyl)-4-[2-(1,2,3,4-tetrahydro-5-naphthoyl)imidazol-1-yl]butyl 1,2,3,4-tetrahydro-5-naphthoate

HRID 1533066Notes

Reaction equation

HRID 1533066 reaction equation
[CH2:1]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([C:11](Cl)=[O:12])[C:5]=2[CH2:4][CH2:3][CH2:2]1.[Cl:14][C:15]1[CH:16]=[C:17]([C@@H:22]([CH2:26][N:27]2[CH:31]=[CH:30][N:29]=[CH:28]2)[CH2:23][CH2:24][OH:25])[CH:18]=[CH:19][C:20]=1[Cl:21].C(N([CH2:37][CH3:38])CC)C>C(#N)C>[CH2:1]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([C:11]([O:25][CH2:24][CH2:23][C@@H:22]([C:17]3[CH:18]=[CH:19][C:20]([Cl:21])=[C:15]([Cl:14])[CH:16]=3)[CH2:26][N:27]3[CH:31]=[CH:30][N:29]=[C:28]3[C:11]([C:6]3[C:5]4[CH2:4][CH2:3][CH2:2][CH2:1][C:10]=4[CH:9]=[CH:37][CH:38]=3)=[O:12])=[O:12])[C:5]=2[CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27531625,6,7,8-Tetrahydronaphthalene-1-carbonyl chlorideHCID 541546783(S)-(3,4-dichlorophenyl)-4-(imidazol-1-yl)butan-1-ol

Product 1

HCID 598865763(S)-(3,4-dichlorophenyl)-4-[2-(1,2,3,4-tetrahydro-5-naphthoyl)imidazol-1-yl]butyl 1,2,3,4-tetrahydro-5-naphthoateYield 72.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1,2,3,4-Tetrahydro-5-naphthoyl chloride (1.70 g) (see Preparation 36) was added dropwise to a suspension of 3(S)-(3,4-dichlorophenyl)-4-(imidazol-1-yl)butan-1-ol (0.90 g) (see Preparation 99) and triethylamine (1.45 g) in anhydrous acetonitrile (15 ml) and the solution stirred at room temperature for 4 days. The solvent was then removed under reduced pressure to give a residue which was partitioned between ethyl acetate and saturated aqueous sodium hydrogen carbonate solution. The phases were separated and the aqueous phase further extracted with ethyl acetate. The organic phases were combined, washed sequentially with water and brine, dried over anhydrous sodium sulphate and the solvent removed under reduced pressure to give a residue which was chromatographed on silica gel eluting with a solvent gradient of 2:1 changing to 0:1, by volume, pentane:ethyl acetate to give 3(S)-(3,4-dichlorophenyl)-4-[2-(1,2,3,4-tetrahydro-5-naphthoyl)imidazol-1-yl]butyl 1,2,3,4-tetrahydro-5-naphthoate (1.38 g) as a gum.

Workup

  1. customThe solvent was then removed under reduced pressure
  2. customto give a residue which
  3. customwas partitioned between ethyl acetate and saturated aqueous sodium hydrogen carbonate solution
  4. customThe phases were separated
  5. extractionthe aqueous phase further extracted with ethyl acetate
  6. washwashed sequentially with water and brine
  7. dry with materialdried over anhydrous sodium sulphate
  8. customthe solvent removed under reduced pressure
  9. customto give a residue which
  10. customwas chromatographed on silica gel eluting with a solvent gradient of 2:1 changing to 0:1, by volume, pentane

Sources & evidence

ORD record
ord-f226241f207e442a87ef41ed801b089d
Source dataset
uspto-grants-2001_03
Patent number
US06207678B1

Reaction notes

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