(2R,3R)-6-hydroxy-4-methylhexane-2,3-diyl dinitrate → 1-[({[(4R,5R)-3-Methyl-4,5-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 889525Notes

Reaction equation

HRID 889525 reaction equation
[N+:1]([O-:16])([O:3][C@@H:4]([C@H:6]([O:12][N+:13]([O-:15])=[O:14])[CH:7]([CH3:11])[CH2:8][CH2:9][OH:10])[CH3:5])=[O:2].[CH2:17]([O:19][C:20]1[N:24]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[C:38]3[N:42]([C:43]([C:56]4[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=4)([C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)[C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)[N:41]=[N:40][N:39]=3)=[CH:28][CH:27]=2)[C:23]2[C:62]([C:66]([O:68][C:69]([CH3:84])([O:71][C:72](OC3C=CC([N+]([O-])=O)=CC=3)=[O:73])[CH3:70])=[O:67])=[CH:63][CH:64]=[CH:65][C:22]=2[N:21]=1)[CH3:18]>C(Cl)Cl>[CH2:17]([O:19][C:20]1[N:24]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[C:38]3[N:42]([C:43]([C:56]4[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=4)([C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)[C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)[N:41]=[N:40][N:39]=3)=[CH:28][CH:27]=2)[C:23]2[C:62]([C:66]([O:68][C:69]([O:71][C:72]([O:10][CH2:9][CH2:8][CH:7]([CH3:11])[C@@H:6]([O:12][N+:13]([O-:15])=[O:14])[C@H:4]([O:3][N+:1]([O-:16])=[O:2])[CH3:5])=[O:73])([CH3:84])[CH3:70])=[O:67])=[CH:63][CH:64]=[CH:65][C:22]=2[N:21]=1)[CH3:18]

Participants

4

Reactant 2

HCID 59549895(2R,3R)-6-hydroxy-4-methylhexane-2,3-diyl dinitrate2×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 866470221-[({[(4R,5R)-3-Methyl-4,5-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 6344DichloromethaneSolvent2×

Procedure

(2R,3R)-6-hydroxy-4-methylhexane-2,3-diyl dinitrate (Intermediate 2, 0.78 g, 3.26 mmol) was added to a stirred 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 4, 1.96 g, 2.17 mmol) in CH2Cl2 (20 mL). The solution was stirred at room temperature overnight. The solution was diluted with CH2Cl2 (20 mL) washed with a solution of NaH2PO4 5% (2×20 mL) and brine. The organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography (Biotage SP1, SNAP 100 g column, TLC method, n-Hexane/EtOAc 6:4, Rf:0.45) affording the title compound that was used without any further purification.

Workup

  1. washwashed with a solution of NaH2PO4 5% (2×20 mL) and brine
  2. dry with materialThe organic layers were dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by flash chromatography (Biotage SP1, SNAP 100 g column, TLC method, n-Hexane/EtOAc 6:4, Rf:0.45)

Sources & evidence

ORD record
ord-a2c297c29b1d48d8be4f791a219808c9
Source dataset
uspto-grants-2012_08
Patent number
US08252825B2

Reaction notes

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