tert-butyl N-methyl-N-(2-oxoethyl)carbamate → tert-Butyl 2-(4-(dimethylamino)-4-phenylpiperidin-1-yl)ethyl(methyl)carbamate

HRID 1500316Notes

Reaction equation

HRID 1500316 reaction equation
[CH3:1][N:2]([CH3:15])[C:3]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.[CH3:16][N:17]([CH2:25][CH:26]=O)[C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21].C(B)#N.[Na]>CO.C(O)(=O)C.CO.C(Cl)(Cl)Cl>[CH3:1][N:2]([CH3:15])[C:3]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:5][N:6]([CH2:26][CH2:25][N:17]([CH3:16])[C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:21])[CH3:23])[CH2:7][CH2:8]1

Participants

7

Reactant 3

HCID 10725881tert-butyl N-methyl-N-(2-oxoethyl)carbamateHCID 57831258N,N-dimethyl-4-phenylpiperidin-4-amineHCID 101953985CID 1019539852×

Product 1

HCID 68408263tert-Butyl 2-(4-(dimethylamino)-4-phenylpiperidin-1-yl)ethyl(methyl)carbamateYield 64.6%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolvent2×HCID 887MethanolSolventHCID 21584188Chloroform methanolSolvent

Conditions

Temperature
0 °C

Procedure

7 g (1 eq) N,N-dimethyl-4-phenylpiperidin-4-amine were added in portions to a solution of 6.5 g (1.5 eq) tert-butyl methyl(2-oxoethyl)carbamate in 60 ml methanol. This reaction mixture was cooled to 0° C., 3.97 g (2.5 eq) sodium cyanoboron hydride were added in portions and then the mixture was stirred for 10 min at room temperature. The reaction mixture obtained was adjusted to a pH of ˜5 with acetic acid and stirred for 12 h at room temperature. The reaction course was monitored by thin-layer chromatography (20% MeOH/CHCl3). As the conversion was still not complete, 1.5 g sodium cyanoboron hydride and acetic acid were added and the reaction mixture was stirred for a further 30 to 45 min. Once the conversion was complete, the methanol was distilled off, 100 ml saturated NaHCO3 solution were added and the mixture obtained was extracted with chloroform (2×200 ml) and the combined organic phases were dried over Na2SO4. Following removal of the solvent under reduced pressure, the residue was purified by column chromatography (silica gel; 5% MeOH/CHCl3). 8 g (64%) of product were obtained in the form of an oil.

Workup

  1. customThe reaction mixture obtained
  2. stirringstirred for 12 h at room temperature
  3. stirringthe reaction mixture was stirred for a further 30 to 45 min
  4. distillationthe methanol was distilled off
  5. addition100 ml saturated NaHCO3 solution were added
  6. customthe mixture obtained
  7. extractionwas extracted with chloroform (2×200 ml)
  8. dry with materialthe combined organic phases were dried over Na2SO4
  9. customremoval of the solvent under reduced pressure
  10. customthe residue was purified by column chromatography (silica gel; 5% MeOH/CHCl3)

Sources & evidence

ORD record
ord-a0734f17f27c4df0b298e3c853566bff
Source dataset
uspto-grants-2015_12
Patent number
US09206156B2

Reaction notes

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