Phosgene → 3-(4-Chlorophenyl)-6-methyl-1,3-dihydrofuro[3,4-c]pyridin-7-yl 3-(nitrooxy)propyl carbonate

HRID 1643425Notes

Reaction equation

HRID 1643425 reaction equation
[N+:1]([O-:8])([O:3][CH2:4][CH2:5][CH2:6][OH:7])=[O:2].[C:9](Cl)(Cl)=[O:10].[CH3:13][C:14]1[N:19]=[CH:18][C:17]2[CH:20]([C:23]3[CH:24]=[CH:25][C:26]([Cl:29])=[CH:27][CH:28]=3)[O:21][CH2:22][C:16]=2[C:15]=1[OH:30].C(N(C(C)C)CC)(C)C>C1COCC1.O>[C:9](=[O:10])([O:7][CH2:6][CH2:5][CH2:4][O:3][N+:1]([O-:8])=[O:2])[O:30][C:15]1[C:16]2[CH2:22][O:21][CH:20]([C:23]3[CH:24]=[CH:25][C:26]([Cl:29])=[CH:27][CH:28]=3)[C:17]=2[CH:18]=[N:19][C:14]=1[CH3:13]

Participants

7

Reactant 4

HCID 6371PhosgeneHCID 54910CicletanineHCID 81531DiisopropylethylamineHCID 100118933-Nitrooxypropanol

Product 1

HCID 446334863-(4-Chlorophenyl)-6-methyl-1,3-dihydrofuro[3,4-c]pyridin-7-yl 3-(nitrooxy)propyl carbonate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-hydroxypropyl nitrate (100 mg, 0.83 mmol) in THF (10 mL) at 0° C. was added phosgene (20% in toluene, 425 mg, 0.86 mmol). After stirring at 0° C. for 45 min, the mixture was allowed to warm to rt. After stirring at rt for 2 hr, the mixture was concentrated. The residue was dissolved in 10 mL CH2Cl2, which was added to a suspension of cicletanine (150 mg, 0.57 mmol) and diisopropylethylamine (185 mg, 1.43 mmol). After stirring at rt over night, the mixture was diluted with H2O and extracted with CH2Cl2. The organic layer was washed with brine, dried over MgSO4 and concentrated. The residue was purified by flash chromatography (Biotage SP1; column 25M; TLC method: n-hexane/ethyl acetate 7/3; Rf=0.35), affording the title product. 1H NMR (500 MHz, CDCl3) δ 8.37 (s, 1H), 7.40-7.28 (m, 4H), 6.29 (s, 1H), 5.42-5.25 (m, 2H), 4.66 (m, 2H), 4.49 (m, 2H), 2.71 (s, 3H), 2.28-2.23 (m, 2H).

Workup

  1. temperatureto warm to rt
  2. stirringAfter stirring at rt for 2 hr
  3. concentrationthe mixture was concentrated
  4. dissolutionThe residue was dissolved in 10 mL CH2Cl2
  5. stirringAfter stirring at rt over night
  6. extractionextracted with CH2Cl2
  7. washThe organic layer was washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography (Biotage SP1; column 25M; TLC method: n-hexane/ethyl acetate 7/3; Rf=0.35)

Sources & evidence

ORD record
ord-c5138b4fbeb64c4d963758cce37b1cfa
Source dataset
uspto-grants-2012_02
Patent number
US08119806B2

Reaction notes

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