Trimethylsilyl iodide → Benzamide

HRID 564407Notes

Reaction equation

HRID 564407 reaction equation
C(OC1C(NC(=O)C[NH:17][C:18](=[O:29])[C:19]2[CH:24]=[CH:23][CH:22]=[C:21](C(F)(F)F)[CH:20]=2)CN(C(OCC2C=CC=CC=2)=O)C1)C1C=CC=CC=1.[Si](I)(C)(C)C>ClCCl>[C:18]([NH2:17])(=[O:29])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 67004437HCID 67004437, compound

Product 1

HCID 2331Benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of benzyl rac-(3R,4R)-3-(benzyloxy)-4-[({[3-(trifluoromethyl)benzoyl]amino}acetyl)amino]pyrrolidine-1-carboxylate in dichloromethane was slowly added TMSI (˜3 equiv.). After 1 hour, all volatiles were removed and the slurry was taken up in acetonitrile (3 mL). 1-(4-methoxyphenyl)piperidin-4-one and sodium triacetoxyborohydride were added and the reaction mixture was stirred overnight. To the mixture was added NaHCO3 (sat. aq., 10 mL) and dichloromethane (10 mL). The organic layer was separated and the aqueous layer was washed with an addition portion of dichloromethane (10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The resulting crude product was subjected to flash chromatography (15% MeOH, 1% NH4OH in EtOAc) to afford N-[2-({(3R,4R)-4-benzyloxy)-1-[1-(4-methoxyphenyl)piperidin-4-yl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-trifluoromethyl)benzamide (55 mg overall) as a white solid. 1H-NMR (CDCl3) δ: 1.98-2.15 (m, 1H), 2.53-2.62 (m, 2H), 3.05-3.19 (m, 2H), 3.33-3.38 (m, 1H), 3.47-3.52 (d, J=12.3 Hz, 2H), 3.63-3.69 (m, 4M), 3.86-3.99 (m, 1H), 4.14-4.22 (m, 3H), 4.52-4.77 (m, 3H), 6.73-6.78 (m, 4H), 7.22-7.35 (m, 5H), 7.47-7.52 (t, J=7.6 Hz, 1H), 7.67-7.70 (d, J=7.5 Hz, 1H), 8.03-8.07 (m, 2H), 8.12 (s, 1H). MS m/z: 611 (M+1)

Workup

  1. customall volatiles were removed
  2. addition1-(4-methoxyphenyl)piperidin-4-one and sodium triacetoxyborohydride were added
  3. additionTo the mixture was added NaHCO3 (sat. aq., 10 mL) and dichloromethane (10 mL)
  4. customThe organic layer was separated
  5. washthe aqueous layer was washed with an addition portion of dichloromethane (10 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-ddfe0386b75b465a8485640fba968060
Source dataset
uspto-grants-2011_11
Patent number
US08067457B2

Reaction notes

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