Potassium Carbonate → {4-[(5-Chloro-3-methyl-pyridin-2-ylmethyl)-amino]-butyl}-(2-fluoro-ethyl)-carbamic acid tert-butyl ester

HRID 251073Notes

Reaction equation

HRID 251073 reaction equation
[C:1]([O:5][C:6](=[O:16])[N:7]([CH2:11][CH2:12][CH2:13][CH2:14][NH2:15])[CH2:8][CH2:9][F:10])([CH3:4])([CH3:3])[CH3:2].[Cl:17][C:18]1[CH:19]=[C:20]([CH3:26])[C:21]([CH:24]=O)=[N:22][CH:23]=1.C([O-])([O-])=O.[K+].[K+].[BH4-].[Na+].C([O-])(O)=O.[Na+]>CO>[C:1]([O:5][C:6](=[O:16])[N:7]([CH2:11][CH2:12][CH2:13][CH2:14][NH:15][CH2:24][C:21]1[C:20]([CH3:26])=[CH:19][C:18]([Cl:17])=[CH:23][N:22]=1)[CH2:8][CH2:9][F:10])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 722140555-Chloro-3-methylpicolinaldehydeHCID 86594767(4-Amino-butyl)-(2-fluoro-ethyl)-carbamic acid tert-butyl ester

Product 1

HCID 86594766{4-[(5-Chloro-3-methyl-pyridin-2-ylmethyl)-amino]-butyl}-(2-fluoro-ethyl)-carbamic acid tert-butyl esterYield 72%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (4-amino-butyl)-(2-fluoro-ethyl)-carbamic acid tert-butyl ester (0.190 g, 0.882 mmol), 5-chloro-3-methyl-pyridine-2-carbaldehyde (0.129 g, 0.882 mmol) and K2CO3 (0.122 g, 0.82) in MeOH (5 mL) was stirred for 16 h. The mixture was filtered through a celite cake and the filtrate was cooled at 0° C. NaBH4 (0.038 g, 1.0 mmol) was added to the filtrate, and the mixture was stirred at for 30 min. Saturated aqueous NaHCO3 (20 mL) was added and MeOH was removed. The aqueous residue was extracted with CH2Cl2 (3×30 mL). The organic extracts were combined and dried over anhydrous Na2SO4. After filtration the solvent was removed by evaporation under vacuum, and the residue was purified by flash chromatography on a silica gel column (200:10:1 CH2Cl2/MeOH/NH4OH), affording {4-[(5-chloro-3-methyl-pyridin-2-ylmethyl)-amino]-butyl}-(2-fluoro-ethyl)-carbamic acid tert-butyl ester as a pale yellow oil (0.215 g, 72%). 1H NMR (CDCl3) δ 1.45 (s, 9H), 1.53-1.66 (m, 4H), 2.30 (s, 3H), 2.71 (t, 2H, J=6.6 Hz), 3.24-3.30 (m, 2H), 3.42-3.52 (m, 2H), 3.84 (s, 2H), 4.40-4.48 (m, 1H), 4.56-4.64 (m, 1H), 7.43 (s, 1H), 8.34 (s, 1H).

Workup

  1. filtrationThe mixture was filtered through a celite cake
  2. stirringthe mixture was stirred at for 30 min
  3. customMeOH was removed
  4. extractionThe aqueous residue was extracted with CH2Cl2 (3×30 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationAfter filtration the solvent
  7. customwas removed by evaporation under vacuum
  8. customthe residue was purified by flash chromatography on a silica gel column (200:10:1 CH2Cl2/MeOH/NH4OH)

Sources & evidence

ORD record
ord-a063955359ea42cbb175d6d9067a7d39
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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