Tetrahydrofuran → Dicyclohexylcarbodiimide

HRID 2380446Notes

Reaction equation

HRID 2380446 reaction equation
[C:1]([N:8]1[CH:12]=[CH:11]N=C1)([N:3]1[CH:7]=[CH:6]N=C1)=O.O1[CH2:17][CH2:16][CH2:15][CH2:14]1>>[CH:12]1([N:8]=[C:1]=[N:3][CH:7]2[CH2:6][CH2:17][CH2:16][CH2:15][CH2:14]2)[CH2:11][CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 682631,1'-Carbonyldiimidazole

Product 1

HCID 10868Dicyclohexylcarbodiimide

Procedure

The compounds of Formula I wherein n is two, R2 is hydrogen, R3 is phenyl or substituted phenyl, and X is a tetrazole are prepared as set forth in Chart V. Compound (32) is prepared according to the method of Paganelli (Tett. Lett. 1991; 32: 2807-2810) by a transition metal catalyzed Michael addition of benzyl cyanide to methyl acrylate. Compound (32) is then treated with (n-Bu)3SnN3 in refluxing dioxane to give the tetrazole (33), which is then alkylated with an alkyl halide, R4 halo, e.g., R4Br, wherein R4 is as defined in Formula I, in acetonitrile employing Et3N as base, giving a mixture of regioisomers (34) and (35) which are separated by flash chromatography. Hydrolysis of each ester with ethanolic NaOH at room temperature gives the respective acids (36) and (38). The acids are then coupled with an appropriate amine of the formula R1NH2 wherein R1 is as defined in Formula I employing carbonyldiimidazole in tetrahydrofuran at room temperature or dicyclohexylcarbodiimide in CH2Cl at 0° C. as coupling agent to give the amides (37) and (39).

Workup

  1. customat room temperature

Sources & evidence

ORD record
ord-7634e0eb4f2d42eba9be6d32502439d8
Source dataset
uspto-grants-1994_11
Patent number
US05366987

Reaction notes

Loading…