Sodium Bicarbonate → {1-[Amino(phenyl)methyl]cyclopentyl}dimethylamine

HRID 20785

Reaction equation

HRID 20785 reaction equation
[CH3:1][N:2]([CH3:10])[C:3]1([C:8]#[N:9])[CH2:7][CH2:6][CH2:5][CH2:4]1.[C:11]1([Li])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[BH4-].[Na+].C(=O)(O)[O-].[Na+]>C1COCC1.C(OCCCC)CCC.CO>[NH2:9][CH:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:3]1([N:2]([CH3:10])[CH3:1])[CH2:7][CH2:6][CH2:5][CH2:4]1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 107730491-(Dimethylamino)cyclopentanecarbonitrileHCID 178506676HCID 178506676, compound

Product 1

HCID 11521393{1-[Amino(phenyl)methyl]cyclopentyl}dimethylamine

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8909Butyl etherSolvent

Procedure

To a solution of 1-(dimethylamino)cyclopentanecarbonitrile D1 (4 g; 28.9 mmol) in THF (30 ml) at −70° C. under argon was added dropwise a solution of phenyllithium in dibutylether (17.7 ml of a 1.8M solution; 32 mmol). The reaction mixture was allowed to warm to room temperature over 3 h., recooled to 0° C. and methanol added (30 ml) followed by careful addition of sodium borohydride (3.3 g; 87 mmol). After stirring at room temperature for 18 h, the reaction mixture was cooled to 0° C. and saturated aqueous sodium bicarbonate added. The organic phase was evaporated and the resulting slurry extracted three times with DCM (3×150 ml). The combined extracts were dried (Na2SO4), and evaporated to afford the crude product as a yellow oil (6.8 g). Half of the crude product was chromatographed on silica gel eluting with DCM-methanol (9/1) and DCM-2M ammonia in methanol mixtures (95/5 to 9/1 to 8/2) to afford the title product as a colourless oil (2.3 g). This oil was dissolved in diethyl ether (20 ml) and hydrogen chloride in diethylether was added at 0° C. After 20 min, the suspension was filtered to give the dihydrochloride salt (2.8 g) of the title product as a white solid. 1H NMR (DMSO) δ: 1.25 (2H, bs), 1.36 (2H, bs), 1.66-2.13 (4H, m), 2.64 (3H, s), 2.79 (3H, s), 4.92 (1H, bs), 7.32 (3H, m), 7.54 (2H, m), 8.95 (3H, bs), 10.82 (1H, bs).

Workup

  1. customrecooled to 0° C.
  2. temperaturethe reaction mixture was cooled to 0° C.
  3. customThe organic phase was evaporated
  4. extractionthe resulting slurry extracted three times with DCM (3×150 ml)
  5. dry with materialThe combined extracts were dried (Na2SO4)
  6. customevaporated
  7. customto afford the crude product as a yellow oil (6.8 g)
  8. customHalf of the crude product was chromatographed on silica gel eluting with DCM-methanol (9/1) and DCM-2M ammonia in methanol mixtures (95/5 to 9/1 to 8/2)

Sources & evidence

ORD record
ord-d4afe683d8ab4955ae9ad2edc26a9583
Source dataset
uspto-grants-2010_06
Patent number
US07745642B2

Linked notes

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