Acetic Acid → 1-(4-Cyclohex-1-enylphenyl)-3-(3,5-dichlorophenyl)-1-{4-[1-hydroxy-2-(2H-tetrazol-5-yl)ethyl]benzyl}urea

HRID 480383Notes

Reaction equation

HRID 480383 reaction equation
COC([N:6]1[N:10]=[N:9][C:8]([CH3:11])=[N:7]1)(C)C.C([Li])CCC.[C:17]1([C:23]2[CH:28]=[CH:27][C:26]([N:29]([CH2:41][C:42]3[CH:47]=[CH:46][C:45]([CH:48]=[O:49])=[CH:44][CH:43]=3)[C:30]([NH:32][C:33]3[CH:38]=[C:37]([Cl:39])[CH:36]=[C:35]([Cl:40])[CH:34]=3)=[O:31])=[CH:25][CH:24]=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH:18]=1.C(O)(=O)C>C1COCC1>[C:17]1([C:23]2[CH:24]=[CH:25][C:26]([N:29]([CH2:41][C:42]3[CH:43]=[CH:44][C:45]([CH:48]([OH:49])[CH2:11][C:8]4[N:9]=[N:10][NH:6][N:7]=4)=[CH:46][CH:47]=3)[C:30]([NH:32][C:33]3[CH:34]=[C:35]([Cl:40])[CH:36]=[C:37]([Cl:39])[CH:38]=3)=[O:31])=[CH:27][CH:28]=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH:18]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 187689071-(4-Cyclohex-1-enylphenyl)-3-(3,5-dichlorophenyl)-1-(4-formylbenzyl)ureaHCID 187689122-(1-Methoxy-1-methylethyl)-5-methyl-2h-tetrazoleHCID 178418339Butyllithium

Product 1

HCID 187689131-(4-Cyclohex-1-enylphenyl)-3-(3,5-dichlorophenyl)-1-{4-[1-hydroxy-2-(2H-tetrazol-5-yl)ethyl]benzyl}urea

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 2-(1-methoxy-1-methylethyl)-5-methyl-2H-tetrazole (1000 mg, 6.41 mmol) in THF (5 ml) cooled to −78° C. on a dry-ice-acetone bath was added dropwise a solution of n-butyl lithium in hexanes (4.0 ml, 1.6 M, 6.4 mmol). The mixture was stirred at −78° C. for 30 min, and at 0° C. for an additional 30 min, then recooled to −78° C. 1-(4-Cyclohex-1-enylphenyl)-3-(3,5-dichlorophenyl)-1-(4-formylbenzyl)urea (250 mg, 0.52 mmol, from step 2, example 12) was then added as a solid, and the mixture was maintained at −78° C. for 20 min. Reaction temperature was raised to 0° C. and the mixture was stirred for 20 min before addition of acetic acid (2 ml). Upon standing, a white solid starts to precipitate, which is collected and washed with cold acetonitrile. The solid is oven dried under vacuum, to yield 582 mg (95%).

Workup

  1. waitat 0° C. for an additional 30 min
  2. customrecooled to −78° C
  3. temperaturethe mixture was maintained at −78° C. for 20 min
  4. customReaction temperature
  5. temperaturewas raised to 0° C.
  6. customa white solid starts to precipitate
  7. customwhich is collected
  8. washwashed with cold acetonitrile
  9. customdried under vacuum
  10. customto yield 582 mg (95%)

Sources & evidence

ORD record
ord-386d29e19ba241d9970b4ec3e4ca4d45
Source dataset
uspto-grants-2003_11
Patent number
US06649641B2

Reaction notes

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