Ethanol → HCID 67054558, compound

HRID 2406239Notes

Reaction equation

HRID 2406239 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14](=O)[CH3:15])=[CH:4][CH:3]=1.[CH2:17]1[O:26][C:20]2([CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[O:19][CH2:18]1.C(O)C.[BH4-].[Na+]>C(OCC)(=O)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[CH:14]([N:23]2[CH2:24][CH2:25][C:20]3([O:26][CH2:17][CH2:18][O:19]3)[CH2:21][CH2:22]2)[CH3:15])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 4311764Sodium borohydrideHCID 201001921-(4'-Chloro[1,1'-biphenyl]-2-yl)ethan-1-one

Product 1

HCID 67054558HCID 67054558, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

To a mixture of 1-(4′-Chloro-biphenyl-2-yl)-ethanone (2.42 g, 10.5 mmol) and 4-piperidone ethylene ketal (1.50 g, 10.5 mmol) and titanium (IV) isopropoxide (5.96 g, 21.0 mmol) is heated up to 75° C. for 3 hours. The reaction is then cooled to room temperature and is added 50 mL of ethanol followed by sodium borohydride (1.19 g, 31.5 mmol) the reaction is then stirred for 18 hours at room temperature and then quench with 50 mL of methanol. The crude reaction is then dissolved in ethyl acetate and then washed with a saturated solution of sodium bicarbonate. The aqueous layer is then extracted 2 times with ethyl acetate. The combined organic layer are then dried on MgSO4 and the solvent is removed under vacuum. The residue is chromatographed on silica gel gel (gradient: heptane/EtOAc; 0 to 60% EtOAc over 15 minutes) to afford 8-[1-(4′-Chloro-biphenyl-2-yl)-ethyl]-1,4-dioxa-8-aza-spiro[4.5]decane (3.6 g, 96%). Found m/z ES+=358.5 (M+H); 1H NMR (400 MHz, CD2Cl2) δ 7.64 (1H, d, J=8.1 Hz), 7.41 (2H, d, J=8.6 Hz), 7.40 (1H, t), 7.30 (2H, J=8.6 Hz), 7.29 (1H, t), 7.18 (1H, d, J=7.6 Hz), 3.90 (4H, s), 3.51 (1H, m), 2.48 (2H, m), 2.36 (2H, m), 1.62 (4H, m), 1.27 (3H, d, J=6.6 Hz).

Workup

  1. temperatureThe reaction is then cooled to room temperature
  2. customquench with 50 mL of methanol
  3. customThe crude reaction
  4. washwashed with a saturated solution of sodium bicarbonate
  5. extractionThe aqueous layer is then extracted 2 times with ethyl acetate
  6. customThe combined organic layer are then dried on MgSO4
  7. customthe solvent is removed under vacuum
  8. customThe residue is chromatographed on silica gel gel (gradient: heptane/EtOAc; 0 to 60% EtOAc over 15 minutes)

Sources & evidence

ORD record
ord-198bf57e278c47cd95bb93c3cf8df179
Source dataset
uspto-grants-2014_08
Patent number
US08809352B2

Reaction notes

Loading…