2-Cyanomethyl-5-(5'-fluoro-2-methoxyphenethyl)tetrahydrofuran → Tetrahydrofuranyl ethylamine, 14

HRID 1919538Notes

Reaction equation

HRID 1919538 reaction equation
[C:1]([CH2:3][CH:4]1[CH2:8][CH2:7][CH:6]([CH2:9][CH2:10][C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=2[O:18][CH3:19])[O:5]1)#[N:2]>N.CO.[Ni]>[NH2:2][CH2:1][CH2:3][CH:4]1[CH2:8][CH2:7][CH:6]([CH2:9][CH2:10][C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=2[O:18][CH3:19])[O:5]1

Participants

5

Reactant 1

HCID 744366842-Cyanomethyl-5-(5'-fluoro-2-methoxyphenethyl)tetrahydrofuran

Product 1

HCID 11587069Tetrahydrofuranyl ethylamine, 14Yield 70%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 222AmmoniaSolventHCID 887MethanolSolvent

Procedure

To a round bottom flask under an atmosphere of Ar was added Raney Ni that was washed with methanol. Compound 12 (80 mg, 0.3 mmol), dissolved in 2 M NH3 in methanol was added to the flask. The flask was evacuated and purged with H2 once. A balloon containing H2 gas was then attached to the flask and the reaction was allowed to stir for 4 h at room temperature. The reaction mixture was filtered through a plug of Celite and the crude product obtained after the removal of the solvent was purified by preparative TLC and eluted with (MeOH/CH2Cl2, 10:90, v:v, Rf=0.1) to give the product (55 mg, 70%) as a 2:1 mixture of trans/cis diastereomers; 1H NMR: (CDCl3, 500 MHz): δ 6.87 (m, 1 H), 6.82 (dd, J=3.0, 8.5 Hz, 1 H), 6.72 (m, 1 H), 4.03 (m, 0.65 H), 3.96 (m, 0.65 H), 3.89 (m, 0.35 H), 3.82 (m, 0.35 H), 3.78 (s, 3 H), 2.68 (m, 1 H), 2.58 (m, 1 H), 2.03 (m, 2 H), 1.83 (bs, 2 H), 1.86-1.6 (m, 4 H), 1.54 (m, 2 H); HRMS (ESI) [M+H]+ calcd for C15H23FNO2 268.1713, found 268.1701; HPLC>96% pure (tR=4.66 min, 40(A):55(B):5(C):0.01(D); tR=5.05 min, 10(A):85(B):5(C):0.01(D)).

Workup

  1. washwas washed with methanol
  2. additionwas added to the flask
  3. customThe flask was evacuated
  4. custompurged with H2 once
  5. additionA balloon containing H2 gas
  6. filtrationThe reaction mixture was filtered through a plug of Celite
  7. customthe crude product obtained
  8. customafter the removal of the solvent
  9. customwas purified by preparative TLC
  10. washeluted with (MeOH/CH2Cl2, 10:90, v:v, Rf=0.1)

Sources & evidence

ORD record
ord-2903862ed70d4fc9a13a47261b1585ef
Source dataset
uspto-grants-2012_05
Patent number
US08168635B2

Reaction notes

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