5,6-Bis(nitrooxy)hexan-1-ol → 1-[({[5,6-bis(nitrooxy)hexyl]oxy}carbonyl)oxy]-1-methylethyl 2-ethoxy-1-{[2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate

HRID 1361916Notes

Reaction equation

HRID 1361916 reaction equation
[N+:1]([O-:15])([O:3][CH2:4][CH:5]([O:11][N+:12]([O-:14])=[O:13])[CH2:6][CH2:7][CH2:8][CH2:9][OH:10])=[O:2].[CH2:16]([O:18][C:19]1[N:23]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[C:37]3[N:41]([C:42]([C:55]4[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=4)([C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=4)[C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)[N:40]=[N:39][N:38]=3)=[CH:27][CH:26]=2)[C:22]2[C:61]([C:65]([O:67][C:68]([CH3:83])([O:70][C:71](OC3C=CC([N+]([O-])=O)=CC=3)=[O:72])[CH3:69])=[O:66])=[CH:62][CH:63]=[CH:64][C:21]=2[N:20]=1)[CH3:17]>ClCCl>[CH2:16]([O:18][C:19]1[N:23]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[C:37]3[N:41]([C:42]([C:55]4[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=4)([C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=4)[C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)[N:40]=[N:39][N:38]=3)=[CH:27][CH:26]=2)[C:22]2[C:61]([C:65]([O:67][C:68]([O:70][C:71]([O:10][CH2:9][CH2:8][CH2:7][CH2:6][CH:5]([O:11][N+:12]([O-:14])=[O:13])[CH2:4][O:3][N+:1]([O-:15])=[O:2])=[O:72])([CH3:83])[CH3:69])=[O:66])=[CH:62][CH:63]=[CH:64][C:21]=2[N:20]=1)[CH3:17]

Participants

4

Reactant 2

HCID 579416215,6-Bis(nitrooxy)hexan-1-ol2×HCID 597787481-methyl-1-{[(4-nitrophenoxy)carbonyl]oxy}ethyl 2-ethoxy-1-{[2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate2×

Product 1

HCID 866225351-[({[5,6-bis(nitrooxy)hexyl]oxy}carbonyl)oxy]-1-methylethyl 2-ethoxy-1-{[2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

6-Hydroxyhexane-1,2-diyl dinitrate (intermediate 1, 0.082 g, 0.36 mmol) and N,N-dimethylaminopyridine (0.029 g, 0.11 mmol) were added to a stirred dichloromethane (3.5 mL) solution of 1-methyl-1-{[(4-nitrophenoxy)carbonyl]oxy}ethyl 2-ethoxy-1-{[2′-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate (intermediate 9, 0.220 g, 0.24 mmol). The solution was stirred at room temperature for 18 hours. Then it was washed with a 5% solution of sodium dihydrogenphosphate (2×10 mL) and brine (10 mL). The organic layer was dried over sodium sulfate, concentrated and purified by flash chromatography (Biotage SP1, 25+M column, TLC method n-hexane/EtOAc 6/4, Rf 0.4), affording the title compound as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.04-8.01 (m, 1H), 7.63-7.61 (m, 2H), 7.46-7.18 (m, 12H), 6.98-6.90 (m, 8H), 6.91 (t, 1H), 6.81 (d, 3H), 6.68 (d, 2H), 5.62 (s, 2H), 5.25-5.23 (m, 1H), 4.72 (dd, 1H), 4.28-4.26 (m, 2H), 4.05 (t, 2H), 1.78-1.52 (m, 10H), 1.49-1.42 (m, 6H).

Workup

  1. washThen it was washed with a 5% solution of sodium dihydrogenphosphate (2×10 mL) and brine (10 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated
  4. custompurified by flash chromatography (Biotage SP1, 25+M column, TLC method n-hexane/EtOAc 6/4, Rf 0.4)

Sources & evidence

ORD record
ord-1b93fdb3435a43a6b5a2b8975979dcf0
Source dataset
uspto-grants-2011_02
Patent number
US07880014B2

Reaction notes

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