Triphenylphosphine → Formate

HRID 1958830Notes

Reaction equation

HRID 1958830 reaction equation
[CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([CH2:21][N:22]([CH2:24][CH3:25])[CH3:23])[CH:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:26])[C:4]=1[OH:27])C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC1(C)[O:53][CH2:52][CH:51](O)[CH2:50][O:49]1.CC[O:58][C:59](/N=N/C(OCC)=O)=[O:60]>C1COCC1.C1(C)C=CC=CC=1>[CH2:24]([N:22]([CH2:21][C:16]1[CH:15]=[C:14]([C:12]2[O:11][N:10]=[C:9]([C:7]3[CH:8]=[C:3]([CH3:1])[C:4]([O:27][CH:51]([CH2:52][OH:53])[CH2:50][OH:49])=[C:5]([CH3:26])[CH:6]=3)[N:13]=2)[CH:19]=[C:18]([CH3:20])[CH:17]=1)[CH3:23])[CH3:25].[CH:59]([O-:60])=[O:58]

Participants

8

Reactant 4

HCID 11776Triphenylphosphine2×HCID 5462977Diethyl azodicarboxylate2×HCID 110298842,2-Dimethyl-1,3-dioxan-5-olHCID 136331245HCID 136331245, compound

Product 2

HCID 283FormateHCID 66932250HCID 66932250, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-ethyl-4-(5-{3-[(ethyl-methyl-amino)-methyl]-5-methyl-phenyl}-[1,2,4]oxadiazol-3-yl)-6-methyl-phenol (100 mg, 273 μmol) in THF (2 mL), PPh3 (107 mg, 409 μmol) followed by 2,2-dimethyl-[1,3]dioxan-5-ol (54 mg, 409 μmol) was added. The mixture was stirred at 0° C. for 10 min before DEAD (178 mg, 409 μmol, 188 μL of a 40% solution in toluene) was added. Stirring was continued at rt for 16 h. Another portion of PPh3 (107 mg, 409 μmol) and DEAD (178 mg, 409 μmol) was added and the mixture was stirred at rt for another hour. The solvent was removed in vacuo and the residue was dissolved in MeCN and separated by prep. HPLC. The acetal intermediate containing fractions were combined and concentrated. The residue was dissolved in MeCN (0.5 mL) and 1N aq. HCl (0.4 mL) and allowed to stand at rt for 10 min before it was again purified by prep. HPLC to give the title compound as a formate salt in the form of a white lyophilisate (71 mg). LC-MS: tR=0.55 min; [M+1]+=440.22; 1H NMR (D6-DMSO): δ 1.06 (t, J=7.0 Hz, 3H), 1.21 (t, J=7.5 Hz, 3H), 2.15 (s, 3H), 2.37 (s, 3H), 2.42-2.48 (m, 5H), 2.78 (q, J=7.5 Hz, 2H), 3.56 (s, 2H), 3.60 (dd, J=11.5 Hz, 5.3 Hz, 2H), 3.64 (dd, J=11.5, 5.0 Hz, 2H), 3.98 (quint, J=5.3 Hz, 1H), 4.77 (br s, 1H), 7.47 (s, 1H), 7.76-7.79 (m, 2H), 7.90 (s, 1H), 7.93 (s, 1H), 8.18 (s, 1H, formate).

Workup

  1. additionwas added
  2. additionwas added
  3. stirringthe mixture was stirred at rt for another hour
  4. customThe solvent was removed in vacuo
  5. dissolutionthe residue was dissolved in MeCN
  6. customseparated by prep
  7. additionThe acetal intermediate containing fractions
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in MeCN (0.5 mL)
  10. waitto stand at rt for 10 min before it
  11. customwas again purified by prep

Sources & evidence

ORD record
ord-1fac647122604ec6b37c47053f627a99
Source dataset
uspto-grants-2013_04
Patent number
US08410151B2

Reaction notes

Loading…