Triethyl phosphite → HCID 53677692, compound

HRID 1281447Notes

Reaction equation

HRID 1281447 reaction equation
[CH2:1]([NH:13][C:14](=[O:36])[C:15]1[CH:20]=[C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=2)[C:18]([O:31][CH2:32][CH2:33]Br)=[C:17]([Br:35])[CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[N-:37]=[N+]=[N-].[Na+].P(OCC)(OCC)OCC>C1C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:1]([NH:13][C:14]([C:15]1[CH:20]=[C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=2)[C:18]([O:31][CH2:32][CH2:33][NH2:37])=[C:17]([Br:35])[CH:16]=1)=[O:36])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]

Participants

6

Reactant 3

HCID 31215Triethyl phosphite2×HCID 33557Sodium Azide2×HCID 22237584HCID 22237584, compound

Product 1

HCID 53677692HCID 53677692, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalyst2×HCID 241BenzeneSolvent

Procedure

To a solution of N-dodecyl-3-bromo-4-(2-bromo-ethoxy)-5-(m-trifluoromethylphenyl)-benzamide (1.431 g, 2.25 mmol, 1 eq) in benzene (2 mL) was added tetrabutyl ammonium bromide (0.053 g, 0.16 mmol, 0.07 eq) and sodium azide (0.216 g, 3.32 mmol, 1.48 eq). The reaction was heated at reflux overnight. Additional tetrabutyl ammonium bromide (0.064 g, 0.20 mmol, 0.09 eq) and sodium azide (0.224 g, 3.45 mmol, 1.53 eq) were required as indicated by TLC. The reaction was cooled to rt and the solids were filtered off. The filtrate was washed with H2O and dried over MgSO4. Triethyl phosphite (0.390 mL, 2.27 mmol, 1.0 eq) was then added to the filtrate and the reaction was stirred overnight at rt. Additional triethyl phosphite (0.780 mL, 4.54 mmol, 2.0 eq) was required. After 48 h, HCl gas was bubbled through the reaction mixture and stirred was continued for 72 h. The reaction was then concentrated in vacuo, dissolved in THF and washed with 2 M HCl. The washes were then adjusted pH 10 with 2.5 M NaOH and were extracted with CH2Cl2. All organics were combined, dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (7 to 12% MeOH:CH2Cl2) to afford the title compound (0.0738 g, 57%) as a colorless oil. 1H NMR (DMSO-d6) δ 8.57 (bt, 1H); 8.12 (d, 1H); 7.90 (m, 3H); 7.80 (d, 1H); 7.73 (dd, 1H); 3.51 (dd, 2H); 3.30 (bs, 2H); 3.23 (dd, 2H); 2.58 (dd, 2H); 1.450 (dd, 2H); 1.25 (m, 18H); 0.83 (t, 3H); IR (film) 3300, 3080, 2920, 2850, 1640, 1600, 1550, 1450, 1330, 1160, 1120, 1080 cm−1; mass spectrum [(+)ESI], m/z 571/573 (M+H)+; Anal. Calcd. for C28H38BrF3N2O2: C, 58.84; H, 6.70; N, 4.90, Found: C, 56.61; H, 6.61; N, 4.71.

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux overnight
  3. filtrationthe solids were filtered off
  4. washThe filtrate was washed with H2O
  5. dry with materialdried over MgSO4
  6. waitAfter 48 h
  7. customHCl gas was bubbled through the reaction mixture
  8. stirringstirred
  9. waitwas continued for 72 h
  10. concentrationThe reaction was then concentrated in vacuo
  11. dissolutiondissolved in THF
  12. washwashed with 2 M HCl
  13. extractionwere extracted with CH2Cl2
  14. dry with materialdried over MgSO4
  15. concentrationconcentrated in vacuo
  16. customThe residue was purified by flash chromatography (7 to 12% MeOH:CH2Cl2)

Sources & evidence

ORD record
ord-a11ea269fb2e43588cfd2868799b510c
Source dataset
uspto-grants-2002_09
Patent number
US06451827B2

Reaction notes

Loading…