Triethylamine → 1,1-Dimethylethyl 4-{[3-({[(3-bromo-4-fluorophenyl)methyl]amino}carbonyl)phenyl]methyl)-1-piperidinecarboxylate

HRID 2080346Notes

Reaction equation

HRID 2080346 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:15]2[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=2)[C:18](O)=[O:19])[CH2:10][CH2:9]1)=[O:7])([CH3:4])[CH3:3].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.C(N(CC)CC)C.Cl.[Br:53][C:54]1[CH:55]=[C:56]([CH2:61][NH2:62])[CH:57]=[CH:58][C:59]=1[F:60]>C(Cl)(Cl)Cl>[Br:53][C:54]1[CH:55]=[C:56]([CH2:61][NH:62][C:18]([C:17]2[CH:16]=[C:15]([CH2:14][CH:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:9][CH2:10]3)[CH:23]=[CH:22][CH:21]=2)=[O:19])[CH:57]=[CH:58][C:59]=1[F:60]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 27249011-(3-Bromo-4-fluorophenyl)methanamine hydrochlorideHCID 450739593-((1-(tert-Butoxycarbonyl)piperidin-4-yl)methyl)benzoic acid

Product 1

HCID 577367091,1-Dimethylethyl 4-{[3-({[(3-bromo-4-fluorophenyl)methyl]amino}carbonyl)phenyl]methyl)-1-piperidinecarboxylateYield 84.6%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To solution of the commercially available 3-[(1-{[(1,1-dimethylethyl)oxy]carbonyl}-4-piperidinyl)methyl]benzoic acid (200 mg, 0.63 mmol) in CHCl3 (5 mL) was added HOBt (90 mg, 0.67 mmol), EDCI (180 mg, 0.94 mmol), and triethylamine (0.2 ml, 1.4 mmol), followed by [(3-bromo-4-fluorophenyl)methyl]amine hydrochloride (151 mg, 0.62 mmol). The resulting mixture was allowed to stir at room temperature for 2 hours then quenched with saturated aq. NaHCO3 (1 mL) was added. The organic layer was separated, dried over Na2SO4 and evaporated to give a residue which was purified by Combiflash® chromatography eluting with hexane/ethyl acetate (95/5 to 70/30 over 15 min.) to give the title compound as white solid (265 mg, 80%). LC/MS: m/z, 505 (M+H), 2.81 min.

Workup

  1. customthen quenched with saturated aq. NaHCO3 (1 mL)
  2. additionwas added
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customto give a residue which
  7. customwas purified by Combiflash® chromatography
  8. washeluting with hexane/ethyl acetate (95/5 to 70/30 over 15 min.)

Sources & evidence

ORD record
ord-ed86467abbea4561bb5b839eff06b059
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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