4-Formylbenzoic acid → HCID 68385262, compound

HRID 529351Notes

Reaction equation

HRID 529351 reaction equation
FC(F)(F)C([N:5]([C@@H:14]1[CH2:16][C@H:15]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:6][CH2:7][CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=O.[CH:25]([C:27]1[CH:35]=[CH:34][C:30]([C:31]([OH:33])=[O:32])=[CH:29][CH:28]=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:17]1([C@@H:15]2[CH2:16][C@H:14]2[NH:5][CH2:6][CH2:7][CH:8]2[CH2:9][CH2:10][N:11]([CH2:25][C:27]3[CH:35]=[CH:34][C:30]([C:31]([OH:33])=[O:32])=[CH:29][CH:28]=3)[CH2:12][CH2:13]2)[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 120884-Formylbenzoic acidHCID 5049666Sodium triacetoxyborohydrideHCID 86708247HCID 86708247, compound

Product 1

HCID 68385262HCID 68385262, compoundYield 62.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)-N-(2-(piperidin-4-yl)ethyl)acetamide (126 mg, 0.370 mmol) in 1,2-dichloroethane (DCE) (2 mL) were added 4-formylbenzoic acid (66.7 mg, 0.444 mmol) and sodium triacetoxyborohydride (157 mg, 0.740 mmol), and the mixture was stirred at room temperature for 18 h. The mixture was quenched with water (2 mL) and extracted with DCM (3×). The extract was dried (Na2SO4) and concentrated. The residue was dissolved into methanol (2 ml) and 1N NaOH aqueous solution (2 mL) was added. The mixture was stirred at room temperature for 1 h and concentrated. The residue was treated with MeOH (3 mL) and filtered. The filtrate was purified using reverse-phase HPLC under the acidic conditions. The resulting TFA salt of the product was treated with 1N HCl and concentrated. The residue was further dried under vacuum to give 87 mg of product as white solid (HCl salt). MS: (M+H)+=379.4. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.25 (q, 1H), 1.46-1.67 (m, 5H), 1.82 (br. s., 2H), 2.87 (br. s., 3H), 3.05 (br. s., 2H), 3.30 (br. s., 2H), 4.34 (d, J=3.79 Hz, 2H), 7.10-7.40 (m, 5H), 7.74 (d, J=8.08 Hz, 2H), 8.00 (d, J=7.83 Hz, 2H), 9.53 (br. s., 2H).

Workup

  1. customThe mixture was quenched with water (2 mL)
  2. extractionextracted with DCM (3×)
  3. dry with materialThe extract was dried (Na2SO4)
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved into methanol (2 ml) and 1N NaOH aqueous solution (2 mL)
  6. additionwas added
  7. stirringThe mixture was stirred at room temperature for 1 h
  8. concentrationconcentrated
  9. additionThe residue was treated with MeOH (3 mL)
  10. filtrationfiltered
  11. customThe filtrate was purified
  12. additionThe resulting TFA salt of the product was treated with 1N HCl
  13. concentrationconcentrated
  14. customThe residue was further dried under vacuum

Sources & evidence

ORD record
ord-fb3f873e71ec4a949730b262cb050c83
Source dataset
uspto-grants-2016_05
Patent number
US09346840B2

Reaction notes

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