Tetrahydrofuran → HCID 11566135, compound

HRID 272936Notes

Reaction equation

HRID 272936 reaction equation
[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH2:22][NH:23][C:24](=O)OC(C)(C)C)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[H-].[H-].[H-].[Li+].[Al+3].C1COCC1>CCOCC>[NH3:1].[CH3:24][NH:23][CH2:22][C:16]1([C:13]2[CH:12]=[CH:11][C:10]([O:9][CH2:8][CH2:7][CH2:6][N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:15][CH:14]=2)[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 21226445Aluminium lithium hydrideHCID 86601899HCID 86601899, compound

Product 2

HCID 222AmmoniaHCID 11566135HCID 11566135, compoundYield 96.7%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

A solution of tert-butyl ({1-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]cyclohexyl}methyl)-carbamate (600 mg, 1.44 mmol) in Et2O (5 mL) was added dropwise to a stirred solution of LiAlH4 (1.0M solution in Et2O, 4.32 mL, 4.32 mmol) at 0° C. THF (5 mL) was added and the reaction mixture heated at reflux overnight. Reaction mixture was cooled to 0° C. quenched with water (0.5 mL), aqueous NaOH (2.0M, 0.5 mL) and water (0.5 mL). Dichloromethane and ethyl acetate were added and the mixture filtered over a short pad of celite, and concentrated in vacuo. The compound was purified by column chromatography on Biotage® silica gel, eluting with dichloromethane:methanol:ammonia, 96:4:0.4 to 90:10:1 to give the title compound as a clear oil (230 mg, 48%). 1H NMR (400 MHz, CDCl3) δ 7.16 (d, 2H), 6.88 (d, 2H), 4.02 (t, 2H), 2.64 (t, 2H) 2.54 (s, 2H), 2.50-2.58 (m, 4H), 2.26 (s, 3H), 2.14-2.08 (m, 2H), 1.98 (pentet, 2H), 1.84-1.76 (m, 4H), 1.68-1.56 (m, 2H), 1.52-1.32 (m, 6H); HRMS (ESI+) 331.2744 (M+H)+.

Workup

  1. temperaturethe reaction mixture heated
  2. temperatureat reflux overnight
  3. customReaction mixture
  4. customquenched with water (0.5 mL), aqueous NaOH (2.0M, 0.5 mL) and water (0.5 mL)
  5. additionDichloromethane and ethyl acetate were added
  6. filtrationthe mixture filtered over a short pad of celite
  7. concentrationconcentrated in vacuo
  8. customThe compound was purified by column chromatography on Biotage® silica gel
  9. washeluting with dichloromethane

Sources & evidence

ORD record
ord-e38fd7263bb04e519c249b649fa14d5d
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

Loading…