Acetic Acid → HCID 86707207, compound

HRID 1476744Notes

Reaction equation

HRID 1476744 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[C:8]([NH:10][C@H:11]([C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=1)[CH3:12])=[O:9].[F:23][C:24]1[CH:33]=[CH:32][C:27]([O:28][CH2:29][CH:30]=O)=[CH:26][CH:25]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[F:23][C:24]1[CH:33]=[CH:32][C:27]([O:28][CH2:29][CH2:30][N:2]2[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]2[C:8]([NH:10][C@H:11]([C:13]2[CH:14]=[CH:15][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:21][CH:22]=2)[CH3:12])=[O:9])=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 110518692-(4-Fluorophenoxy)acetaldehydeHCID 86707208HCID 86707208, compound

Product 1

HCID 86707207HCID 86707207, compoundYield 70.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Stir a mixture of methyl 4-[(1S)-1-[[(2R)-piperidine-2-carbonyl]amino]ethyl]benzoate hydrochloride (650 mg, 1.99 mmol) and 2-(4-fluorophenoxy)acetaldehyde (337 mg, 2.19 mmol) in DCE (9.9 mL) at room temperature for 30 min. Add acetic acid (0.113 mL, 1.99 mmol) and sodium triacetoxyborohydride (590 mg, 2.78 mmol) and stir at room temperature for three days. Quench the reaction with saturated aqueous NaHCO3 (25 mL) and extract the aqueous layer with EtOAc (2×25 mL). Wash the combined organic layers with saturated aqueous NaCl (25 mL), then dry the organic phase over MgSO4, filter, and concentrate under reduced pressure. Subject the resulting oil to flash chromatography on silica gel, eluting with a gradient of 0% to 100% EtOAc/hexanes. Concentrate the fractions containing the desired product under reduced pressure to provide the title compound as a white solid (600 mg, 70% yield). Mass spectrum (m/z) 429 (M+H)+, 451 (M+Na)+.

Workup

  1. customQuench
  2. customthe reaction with saturated aqueous NaHCO3 (25 mL)
  3. extractionextract the aqueous layer with EtOAc (2×25 mL)
  4. washWash the combined organic layers with saturated aqueous NaCl (25 mL)
  5. dry with materialdry the organic phase over MgSO4
  6. filtrationfilter
  7. concentrationconcentrate under reduced pressure
  8. washeluting with a gradient of 0% to 100% EtOAc/hexanes
  9. concentrationConcentrate the fractions
  10. additioncontaining the desired product under reduced pressure

Sources & evidence

ORD record
ord-b3b1e6ea09cd47ea912360d7a83b5a77
Source dataset
uspto-grants-2016_08
Patent number
US09402838B2

Reaction notes

Loading…