Dichloromethane → (2-Butyl-4-chloro-1-((2'-(1-trityl-1H-tetraazol-5-YL)(1,1'-biphenyl)-4-YL)methyl)-1H-imidazol-5-YL)methanol

HRID 465849Notes

Reaction equation

HRID 465849 reaction equation
C[Sn]([N:5]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2[CH:21]=[CH:20][C:19]([CH2:22][N:23]3[C:27]([CH2:28][OH:29])=[C:26]([Cl:30])[N:25]=[C:24]3[CH2:31][CH2:32][CH2:33][CH3:34])=[CH:18][CH:17]=2)=[N:8][N:7]=[N:6]1)(C)C.C(Cl)Cl.[OH-].[Na+].[C:40]1([C:46](Cl)([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>O.O1CCCC1>[C:40]1([C:46]([N:5]2[C:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[C:16]3[CH:21]=[CH:20][C:19]([CH2:22][N:23]4[C:27]([CH2:28][OH:29])=[C:26]([Cl:30])[N:25]=[C:24]4[CH2:31][CH2:32][CH2:33][CH3:34])=[CH:18][CH:17]=3)=[N:8][N:7]=[N:6]2)([C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)[C:53]2[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=2)[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 6456Trityl chloride2×HCID 14798Sodium Hydroxide3×HCID 144256651-[(2'-(Trimethylstannyltetrazol-5-yl)biphenyl-4-yl)methyl]-2-butyl-4-chloro-5-hydroxymethylimidazole

Product 1

HCID 11643218(2-Butyl-4-chloro-1-((2'-(1-trityl-1H-tetraazol-5-YL)(1,1'-biphenyl)-4-YL)methyl)-1H-imidazol-5-YL)methanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-[(2'-(Trimethylstannyltetrazol-5-yl)-biphenyl-4-yl)methyl]-2-butyl-4-chloro-5-hydroxymethylimidazole (1.046 Kg), methylene chloride (5.00 L), tetrahydrofuran (0.85 L) and 10N sodium hydroxide (192 ml) were charged to a 12 liter round-bottomed flask equipped with mechanical stirrer, condenser with N2 inlet, and thermometer. After stirring five minutes at room temperature, triphenylmethyl chloride (0.530 Kg) was added and the mixture stirred three hours. 10N Sodium hydroxide (20 ml) and additional triphenylmethyl chloride (50 g) were added and the mixture stirred overnight. Deionized (D.I.) water (3.70 L) and 10N sodium hydroxide (30 ml) were added and the phases allowed to separate. The organic phase was washed twice with 2.0 L portions of water, dried with sodium sulfate (100 g) and filtered into a 12 L round-bottomed flask equipped for distillation. Methylene chloride (~2.0 L) was distilled. Heating was discontinued and heptane (5.0 L) was added. The resulting slurry was stirred at ambient temperature over the weekend (~68 hours). The mixture was cooled to ~5° C. and the product isolated by vacuum filtration, washed with heptane (1.0 L) and dried 48 hours in in vacuo at 40°-50° C. Yield: 959.5 g, 80%. M.P.: 197°-169° C. Purity by HPLC: 99.8%.

Workup

  1. customequipped with mechanical stirrer, condenser with N2 inlet
  2. stirringthe mixture stirred three hours
  3. stirringthe mixture stirred overnight
  4. customto separate
  5. washThe organic phase was washed twice with 2.0 L portions of water
  6. dry with materialdried with sodium sulfate (100 g)
  7. filtrationfiltered into a 12 L round-bottomed flask
  8. customequipped for distillation
  9. distillationMethylene chloride (~2.0 L) was distilled
  10. temperatureHeating
  11. additionheptane (5.0 L) was added
  12. stirringThe resulting slurry was stirred at ambient temperature over the weekend (~68 hours)
  13. temperatureThe mixture was cooled to ~5° C.
  14. customthe product isolated by vacuum filtration
  15. washwashed with heptane (1.0 L)
  16. customdried 48 hours in in vacuo at 40°-50° C

Sources & evidence

ORD record
ord-2fe057c42ac1484f959179e31d96ba4b
Source dataset
uspto-grants-1992_10
Patent number
US05153197

Reaction notes

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