Acetic Anhydride → Telmisartan

HRID 2095082Notes

Reaction equation

[CH:1]([O-:3])=[O:2].[Li+].C(N(C(C)C)CC)(C)C.C(OC(=O)C)(=O)C.I[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:28]1[CH:33]=[CH:32][C:31]([CH2:34][N:35]2[C:39]3[CH:40]=[C:41]([C:45]4[N:49]([CH3:50])[C:48]5[CH:51]=[CH:52][CH:53]=[CH:54][C:47]=5[N:46]=4)[CH:42]=[C:43]([CH3:44])[C:38]=3[N:37]=[C:36]2[CH2:55][CH2:56][CH3:57])=[CH:30][CH:29]=1.[Li+].[Cl-]>CN(C)C=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:57][CH2:56][CH2:55][C:36]1[N:35]([CH2:34][C:31]2[CH:30]=[CH:29][C:28]([C:23]3[CH:22]=[CH:27][CH:26]=[CH:25][C:24]=3[C:1]([OH:3])=[O:2])=[CH:33][CH:32]=2)[C:39]2[CH:40]=[C:41]([C:45]3[N:49]([CH3:50])[C:48]4[CH:51]=[CH:52][CH:53]=[CH:54][C:47]=4[N:46]=3)[CH:42]=[C:43]([CH3:44])[C:38]=2[N:37]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of lithium formate (262 mg, 3 eq), diisopropylethylamine (DIEA; 0.58 mL, 2 eq), acetic anhydride (0.32 mL, 2 eq) in anhydrous dimethylformamide (DMF; 2 mL) was stirred at room temperature for 1 hour. Then, 3′-(2′-iodo-biphenyl-4-ylmethyl)-1,7′-dimethyl-2′-propyl-1H,3′H-[2,5′]bibenzoimidazolyl (1 g, 1.68 mmol), Pd2(dba)3 (38 mg, 0.025 eq, dba is dibenzylideneacetone), LiCl (211 mg, 3 eq) in anhydrous DMF (4 mL) were added. The reaction mixture was stirred at 80° C. for 3 h, filtered and after cooling poured into 1.2 mL of water, stirred for 15 minutes, product filtered, washed with water and dried in vacuo to yield telmisartan.

Workup

filtrationfiltered
temperatureafter cooling
additionpoured into 1.2 mL of water
stirringstirred for 15 minutes
filtrationproduct filtered
washwashed with water
customdried in vacuo

Sources & evidence

ORD record: ord-d5ed29671274491b92a430f09d4484d4
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445693B2

Reaction notes

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