Diisopropylethylamine → {3-[5-(4-Benzyloxy-3-ethyl-5-methyl-phenyl)-[1,3,4]oxadiazol-2-yl]-5-methyl-benzyl}-ethyl-methyl-amine

HRID 1958834Notes

Reaction equation

HRID 1958834 reaction equation
[CH2:1]([N:3]([CH2:5][C:6]1[CH:7]=[C:8]([CH:12]=[C:13]([CH3:15])[CH:14]=1)[C:9]([OH:11])=O)[CH3:4])[CH3:2].CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[CH2:58]([O:65][C:66]1[C:75]([CH3:76])=[CH:74][C:69]([C:70]([NH:72][NH2:73])=O)=[CH:68][C:67]=1[CH2:77][CH3:78])[C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>C1COCC1.CC(=O)OCC>[CH2:58]([O:65][C:66]1[C:75]([CH3:76])=[CH:74][C:69]([C:70]2[O:11][C:9]([C:8]3[CH:7]=[C:6]([CH:14]=[C:13]([CH3:15])[CH:12]=3)[CH2:5][N:3]([CH2:1][CH3:2])[CH3:4])=[N:73][N:72]=2)=[CH:68][C:67]=1[CH2:77][CH3:78])[C:59]1[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 592020264-Benzyloxy-3-ethyl-5-methyl-benzoic acid hydrazideHCID 669323243-[(Ethyl-methyl-amino)-methyl]-5-methyl-benzoic acid

Product 1

HCID 66932343{3-[5-(4-Benzyloxy-3-ethyl-5-methyl-phenyl)-[1,3,4]oxadiazol-2-yl]-5-methyl-benzyl}-ethyl-methyl-amineYield 89.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 3-[(ethyl-methyl-amino)-methyl]-5-methyl-benzoic acid (750 mg, 3.62 mmol) in THF (10 mL), DIPEA (940 mg, 7.24 mmol) and PyBOP (1.88 g, 3.62 mmol) was added. The mixture was stirred at rt for 1 h before 4-benzyloxy-3-ethyl-5-methyl-benzoic acid hydrazide (2.06 g, 3.62 mmol) was added. The mixture was stirred at rt for 1 h and was then diluted with EA and washed with sat. aq. NaHCO3 solution. The org. phase was collected, dried over MgSO4, filtered and concentrated. The residue was dissolved in THF and Burgess reagent (1.03 g, 4.34 mmol) was added. The mixture was stirred at 110° C. under microwave irradiation for 12 min. The mixture was cooled to rt, diluted with EA and washed with water. The org. phase was separated and concentrated. The crude product is purified by CC on silica gel eluting with DCM:MeOH 9:1 to 5:1 to give {3-[5-(4-benzyloxy-3-ethyl-5-methyl-phenyl)-[1,3,4]oxadiazol-2-yl]-5-methyl-benzyl}-ethyl-methyl-amine as a pale yellow oil (1.48 g). LC-MS: tR=0.96 min; [M+1]+=456.13.

Workup

  1. additionwas added
  2. washwashed with sat. aq. NaHCO3 solution
  3. customphase was collected
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in THF
  8. stirringThe mixture was stirred at 110° C. under microwave irradiation for 12 min
  9. temperatureThe mixture was cooled to rt
  10. washwashed with water
  11. customphase was separated
  12. concentrationconcentrated
  13. customThe crude product is purified by CC on silica gel eluting with DCM:MeOH 9:1 to 5:1

Sources & evidence

ORD record
ord-db7642b4d78b43acb0d9a3b76dbc1fd5
Source dataset
uspto-grants-2013_04
Patent number
US08410151B2

Reaction notes

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