Cesium carbonate → 1-({[(1R,3S,4S)-3-methoxy-4-(nitrooxy)cyclopentyl]carbonyl}oxy)ethyl 2-ethoxy-1-{[2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate

HRID 2067145Notes

Reaction equation

HRID 2067145 reaction equation
[CH2:1]([O:3][C:4]1[N:8]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]3[N:26]([C:27]([C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[N:25]=[N:24][N:23]=3)=[CH:12][CH:11]=2)[C:7]2[C:46]([C:50]([OH:52])=[O:51])=[CH:47][CH:48]=[CH:49][C:6]=2[N:5]=1)[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:59][O:60][C@@H:61]1[C@@H:65]([O:66][N+:67]([O-:69])=[O:68])[CH2:64][C@H:63]([C:70]([O:72][CH:73](Cl)[CH3:74])=[O:71])[CH2:62]1>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[CH2:1]([O:3][C:4]1[N:8]([CH2:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]3[N:26]([C:27]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)([C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=4)[C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=4)[N:25]=[N:24][N:23]=3)=[CH:14][CH:15]=2)[C:7]2[C:46]([C:50]([O:52][CH:73]([O:72][C:70]([C@H:63]3[CH2:64][C@H:65]([O:66][N+:67]([O-:69])=[O:68])[C@@H:61]([O:60][CH3:59])[CH2:62]3)=[O:71])[CH3:74])=[O:51])=[CH:47][CH:48]=[CH:49][C:6]=2[N:5]=1)[CH3:2]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 103125632-Ethoxy-1-((2'-(1-(triphenylmethyl)-1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl)-1H-benzimidazole-7-carboxylic acidHCID 593640921-chloroethyl (1R,3S,4S)-3-methoxy-4-(nitrooxy)cyclopentanecarboxylate2×

Product 1

HCID 866423841-({[(1R,3S,4S)-3-methoxy-4-(nitrooxy)cyclopentyl]carbonyl}oxy)ethyl 2-ethoxy-1-{[2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 2-ethoxy-1-{[2′-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylic acid (2180 mg, 3.19 mmol), cesium carbonate (2150 mg, 6.60 mmol), and tetrabutylammonium hydrogen sulfate (538 mg, 1.59 mmol) was charged with a N,N-dimethylformamide (10 mL) solution of 1-chloroethyl (1R,3S,4S)-3-methoxy-4-(nitrooxy)cyclopentanecarboxylate (intermediate 2, 834 mg, 3.11 mmol). The reaction mixture was heated at 40° C. for 16 hours, and the reaction mixture was purified by column chromatography, eluting with 10/90→70/30 ethyl acetate/hexanes to give the title compound as a white solid. 1H NMR (500 MHz, CDCl3) δ 1.36 (d, J=5.5 Hz, 3H, D1), 1.36 (d, J=5.5 Hz, 3H, D2), 1.41 (t, J=7.1 Hz, 3H), 1.94-2.05 (m, 2H), 2.19-2.27 (m, 1H), 2.46-2.54 (m, 1H), 2.76-2.87 (m, 1H), 3.30 (s, 3H, D1), 3.30 (s, 3H, D2), 3.76 (q, J=4.1 Hz, 1H), 4.61 (q, J=7.1 Hz, 2H, D1), 4.61 (q, J=7.1 Hz, 2H, D2), 5.23 (t, J=6.0 Hz, 1H), 5.53 (d, J=16.0 Hz, 1H), 5.58 (d, J=16.0 Hz, 1H), 6.75 (d, J=6.9 Hz, 2H), 6.88-6.95 (m, 7H), 6.98 (d, J=8.0 Hz, 2H), 7.17 (dt, J=2.0, 7.8 Hz, 1H), 7.23 (t, J=7.7 Hz, 6H), 7.26-7.34 (m, 4H), 7.40-7.48 (m, 2H), 7.54 (dd, J=1.1, 8.0 Hz, 1H), 7.76 (d, J=7.7 Hz, 1H), 7.86 (d, J=7.8 Hz, 1H); LC-MS: m/z 913.6 (M+H).

Workup

  1. customthe reaction mixture was purified by column chromatography
  2. washeluting with 10/90→70/30 ethyl acetate/hexanes

Sources & evidence

ORD record
ord-7717ae00fb964892a0913225d8980d3b
Source dataset
uspto-grants-2012_10
Patent number
US08293777B2

Reaction notes

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