Hydrochloric Acid → (2-{5-[2-(5-Fluoro-2-methoxy-phenyl)-ethyl]-tetrahydro-furan-2-yl}-ethyl)-methyl-amine

HRID 1919541Notes

Reaction equation

HRID 1919541 reaction equation
C(O[C:4](=O)[NH:5][CH2:6][CH2:7][CH:8]1[CH2:12][CH2:11][CH:10]([CH2:13][CH2:14][C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=2[O:22][CH3:23])[O:9]1)C.[H-].[H-].[H-].[H-].[Li+].[Al+3].Cl.[OH-].[Na+]>C1COCC1>[F:21][C:19]1[CH:18]=[CH:17][C:16]([O:22][CH3:23])=[C:15]([CH2:14][CH2:13][CH:10]2[O:9][CH:8]([CH2:7][CH2:6][NH:5][CH3:4])[CH2:12][CH2:11]2)[CH:20]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 25258808(2-{5-[2-(5-Fluoro-2-methoxy-phenyl)-ethyl]-tetrahydro-furan-2-yl}-ethyl)-carbamic ethyl ester

Product 1

HCID 25258809(2-{5-[2-(5-Fluoro-2-methoxy-phenyl)-ethyl]-tetrahydro-furan-2-yl}-ethyl)-methyl-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Into a flame dried round bottom flask, purged with Ar(g), was placed 23 (112 mg, 0.33 mmol, 1.0 eq) and anhydrous THF (1.6 mL). The flask was cooled with an ice bath and stirred for 15 min. LAH (1.0 M, 1.32 mL, 1.32 mmol, 4.0 eq) was then slowly added via syringe over a period of 5 min. The reaction was allowed to warm to rt and stirred an additional 4 hrs. The reaction was then stopped with ice cold MeOH and then stirred for an additional 15 min at rt. The resulting solution was acidified with 1N HCl(aq) and then transferred to a beaker and then made basic with 10 M NaOH(aq). The basic solution was then extracted with diethyl ether (3×20 mL) and then the organic layer was washed with brine. The diethyl ether extract was dried over Mg2SO4 for 15 min and then filtered and concentrated to oil under reduced pressure to afford the crude product. The oil was purified with preparative TLC (developed with MeOH/CH2Cl2, 5:95, v:v, Rf 0.05); 1H NMR (CDCl3, 500 MHz) 6.87-6.82 (m, 2 H), 6.74-6.71 (m, 1 H), 4.05-3.77 (m, 2 H), 3.78 (s, 3 H), 2.71-2.56 (m, 5 H), 2.08-1.51 (m, 10 H); HRMS (ESI) [M+H]+ calcd for C16H25FNO2 282.3784, found 282.3762; HPLC>97% pure (tR=30.23 min, 100(A):0.5(D); tR=26.05 min, 90(A):10(C):0.5(D)).

Workup

  1. customInto a flame dried round bottom flask
  2. custompurged with Ar(g)
  3. temperatureThe flask was cooled with an ice bath
  4. stirringstirred an additional 4 hrs
  5. stirringstirred for an additional 15 min at rt
  6. extractionThe basic solution was then extracted with diethyl ether (3×20 mL)
  7. washthe organic layer was washed with brine
  8. extractionThe diethyl ether extract
  9. dry with materialwas dried over Mg2SO4 for 15 min
  10. filtrationfiltered
  11. concentrationconcentrated to oil under reduced pressure

Sources & evidence

ORD record
ord-7e51249db72242b39dedaf6d1baf3859
Source dataset
uspto-grants-2012_05
Patent number
US08168635B2

Reaction notes

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