Hydrochloric Acid → 5-(4'-dimethoxymethyl-biphenyl-2-yl)-2-(tetrahydro-pyran-2-yl)2H-tetrazole

HRID 644927Notes

Reaction equation

HRID 644927 reaction equation
Cl[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[N:10][N:11]([CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)[N:12]=1.ClC1C=CC=CC=1C1N(C2CCCCO2)N=NN=1.[CH3:37][O:38][CH:39]([O:48][CH3:49])[C:40]1[CH:45]=[CH:44][C:43]([Mg]Br)=[CH:42][CH:41]=1.Cl.ClC1C=CC=CC=1C1NN=NN=1.N1C(C2C=CC=CC=2C2C=CC(C=O)=CC=2)=NN=N1.CO>O1CCCC1>[CH3:49][O:48][CH:39]([O:38][CH3:37])[C:40]1[CH:41]=[CH:42][C:43]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[C:8]2[N:9]=[N:10][N:11]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][O:14]3)[N:12]=2)=[CH:44][CH:45]=1

Participants

9

Reactant 7

HCID 313Hydrochloric AcidHCID 887MethanolHCID 675464055-(2-chlorophenyl)-1-(tetrahydropyran-2-yl)-1H-tetrazoleHCID 675468845-(2-Chlorophenyl)-2-(oxan-2-yl)-2H-tetrazoleHCID 178478026HCID 178478026, compoundHCID 178499441HCID 178499441, compound2×HCID 1785194042'-(1H-Tetrazol-5-yl)-1,1'-biphenyl-4-carboxaldehyde (Losartan Impurity)

Product 1

HCID 686269945-(4'-dimethoxymethyl-biphenyl-2-yl)-2-(tetrahydro-pyran-2-yl)2H-tetrazole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
15 °C

Procedure

A mixture of 5-(2-chlorophenyl)-2-(tetrahydropyran-2-yl)-2H-tetrazole and 5-(2-chlorophenyl) 1-(tetrahydropyran-2-yl)-1H-tetrazole (94% content; 4.22 g; 15.0 mmol; same batch as used in Example 7) is dissolved in anhydrous tetrahydrofuran (2.8 mL) under an inert atmosphere. The vigorously stirred resulting suspension is cooled to about 15° C. and a 0.96 M 4-(dimethoxymethyl)phenylmagnesium bromide solution (18 mL; 17.3 mmol; same batch as used in Example 7) is added over one hour while keeping the temperature below 25° C. by external cooling. The brown reaction mixture is agitated at room temperature for 22 hours. After that, HPLC analysis is done on a sample which is, as usual, hydrolyzed with dilute aqueous hydrochloric acid. The analysis shows mainly unconverted starting material (detected as 5-(2-chlorophenyl)-1H-tetrazole) and less than 0.25 area % of C—C-coupling product (detected as 2′-(1H-tetrazol-5-yl)biphenyl-4-carbaldehyde). Finally, when methanol (1.2 mL; 30 mmol) is added to the mixture, an unusually strong exotherm is observed which indicates that most of the 4-(dimethoxymethyl)phenylmagnesium bromide is still present after a total reaction time of 23 hours.

Workup

  1. customresulting suspension
  2. customthe temperature below 25° C.
  3. stirringThe brown reaction mixture is agitated at room temperature for 22 hours
  4. customafter a total reaction time of 23 hours

Sources & evidence

ORD record
ord-6f407adb4bcb4d2e920c7964074bdf0a
Source dataset
uspto-grants-2010_04
Patent number
US07700784B2

Reaction notes

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