Dimethyl Sulfate → HCID 54145076, compound

HRID 1757243Notes

Reaction equation

HRID 1757243 reaction equation
[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([CH2:13][O:14][C@@H:15]2[CH2:20][CH2:19][CH2:18][N:17]([CH2:21][C:22]3[NH:26][N:25]=[N:24][N:23]=3)[C@@H:16]2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[Na+].S(OC)(O[CH3:41])(=O)=O>O>[F:12][C:9]([F:11])([F:10])[C:7]1[CH:6]=[C:5]([CH2:13][O:14][C@@H:15]2[CH2:20][CH2:19][CH2:18][N:17]([CH2:21][C:22]3[N:23]=[N:24][N:25]([CH3:41])[N:26]=3)[C@@H:16]2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:4]=[C:3]([C:2]([F:1])([F:33])[F:34])[CH:8]=1

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 14798Sodium HydroxideHCID 178506224HCID 178506224, compound

Product 1

HCID 54145076HCID 54145076, compoundYield 19.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
96 °C

Procedure

The compound of Example 7 (500 mg) was suspended in water (4 ml) and sodium hydroxide (44 mg) added. This was heated to an external temperature of 96° C. and dimethyl sulphate (65 mg) added. The reaction mixture was allowed to stir under nitrogen at 96° C. for 1 h after which time stirring was continued for 24 h at 5° C. After this time, the product was extracted into dichloromethane and washed with water and brine. The organic layer was dried (MgSO4) and evaporated. The residue was purified on silica using medium pressure chromatography (Lobar), and eluted with 25% ethyl acetate in petrol. The first compound to be eluted was isolated, and this afforded the product (50 mg) as a crystalline solid, which was recrystallised from ether/hexane to afford white crystals: mp 139°-141° C. 1H NMR (360 MHz, DMSO) d 1.44-1.51 (2H, m, CH2), 1.79-1.82 (1H, m, CHH), 2.12-2.15 (1H, m, CHH), 2.19-2.25 (1H, m, CHHN), 2.97-3.00 (1H, m, CHHN), 3.37 (1H, d, J=14 Hz, N--CHH-tetrazole), 3.52 (1H, s, NCHCHO), 3.58 (1H, s, NCHCHO), 3.81 (1H, d, J=14 Hz, N--CHH-tetrazole), 4.03 (1H, d, J=13 Hz, OCHH), 4.31 (3H, s, CH3), 4.60 (1H, d, J=13 Hz, OCHH), 7.23-7.33 (3H, m, ArH), 7.49-7.51 (2H, m, ArH), 7.68 (2H, s, ArH), 7.93 (1H, s, ArH); MS (CI+) m/z 500 ((M+1)+, 100%). Found: C, 55.56; H, 4.76; N, 14.20. Calculated for C23H23N5OF6 : C, 55.31; H, 4.64; N, 14.02%.

Workup

  1. additionadded
  2. stirringstirring
  3. waitwas continued for 24 h at 5° C
  4. extractionAfter this time, the product was extracted into dichloromethane
  5. washwashed with water and brine
  6. dry with materialThe organic layer was dried (MgSO4)
  7. customevaporated
  8. customThe residue was purified on silica using medium pressure chromatography (Lobar)
  9. washeluted with 25% ethyl acetate in petrol
  10. washThe first compound to be eluted
  11. customwas isolated

Sources & evidence

ORD record
ord-f48708a54ee140ac8857a19d806b0003
Source dataset
uspto-grants-1995_08
Patent number
US05444074

Reaction notes

Loading…