Pyridine → 2,3-bis(nitrooxy)propyl (2Z)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-[4-(methylsulfonyl)phenyl]-3-phenylbut-2-en-1-yl carbonate

HRID 1437590Notes

Reaction equation

HRID 1437590 reaction equation
[N+:1]([O-:12])([O:3][CH2:4][CH:5]([O:8][N+:9]([O-:11])=[O:10])[CH2:6][OH:7])=[O:2].ClC(Cl)(O[C:17](=[O:23])[O:18][C:19](Cl)(Cl)Cl)Cl.N1C=CC=CC=1.[Si:31]([O:38][CH2:39]/[C:40](/[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[C:41](/[C:44]1[CH:49]=[CH:48][C:47]([S:50]([CH3:53])(=[O:52])=[O:51])=[CH:46][CH:45]=1)\CO)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32]>ClCCl>[C:17](=[O:23])([O:18][CH2:19]/[C:41](/[C:44]1[CH:49]=[CH:48][C:47]([S:50]([CH3:53])(=[O:52])=[O:51])=[CH:46][CH:45]=1)=[C:40](/[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)\[CH2:39][O:38][Si:31]([C:34]([CH3:37])([CH3:35])[CH3:36])([CH3:33])[CH3:32])[O:7][CH2:6][CH:5]([O:8][N+:9]([O-:11])=[O:10])[CH2:4][O:3][N+:1]([O-:12])=[O:2]

Participants

6

Reactant 4

HCID 1049Pyridine2×HCID 79076Glyceryl 1,2-DinitrateHCID 94429TriphosgeneHCID 58787782(2Z)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-[4-(methylsulfonyl)phenyl]-3-phenylbut-2-en-1-ol

Product 1

HCID 866234332,3-bis(nitrooxy)propyl (2Z)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-[4-(methylsulfonyl)phenyl]-3-phenylbut-2-en-1-yl carbonateYield 127.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a −78° C. solution of 2.5 g (13.7 mmol) of 3-hydroxypropane-1,2-diyl dinitrate in 20 mL dichloromethane was added 1.36 g (4.57 mmol) of triphosgene followed by 1.22 mL (15.10 mmol) of pyridine. The resulting mixture was stirred for 5 min at −78° C. then warmed to rt for 15 min upon which the solution turned from cloudy to clear. The above solution was then transferred slowly to a −78° C. solution of 5.64 g (13.04 mmol) (2Z)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-[4-(methylsulfonyl)phenyl]-3-phenylbut-2-en-1-ol and 1.11 mL (13.73 mmol) pyridine in 20 mL of dichloromethane. After complete addition, the reaction mixture was warmed to 0° C. and stirred for an additional 25 min. The reaction was then quenched with NH4Cl (aq) and the organic layer separated, dried (Na2SO4), filtered and concentrated in vacuo to give a yellow oil. Purification by flash chromatography over silica gel (10-80% EtOAc/hexane) afforded 3.73 g of the title compound as an oil. 1H NMR (500 MHz, acetone-d6): δ 7.72 (d, 2H), 7.38 (d, 2H), 7.18-7.08 (m, 5H), 5.79-5.75 (m, 1H), 5.35 (s, 2H), 5.05 (dd, 1H), 4.87 (dd, 1H), 4.80 (s, 2H), 4.66 (dd, 1H), 4.49 (dd, 1H), 3.05 (s, 3H), 0.84 (s, 9H), 0.01 (s, 6H).

Workup

  1. temperaturethen warmed to rt for 15 min upon which the solution
  2. customwas then transferred slowly to a −78° C.
  3. additionAfter complete addition
  4. temperaturethe reaction mixture was warmed to 0° C.
  5. stirringstirred for an additional 25 min
  6. customThe reaction was then quenched with NH4Cl (aq)
  7. customthe organic layer separated
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give a yellow oil
  12. customPurification by flash chromatography over silica gel (10-80% EtOAc/hexane)

Sources & evidence

ORD record
ord-7d3c3da1ddef4b92bb646ad564b0c7c5
Source dataset
uspto-grants-2009_11
Patent number
US07622501B2

Reaction notes

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