1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-(tert-butoxycarbonyl)-4-[[N-(3-(trifluoromethyl)benzoyl)glycyl]aminomethyl]piperidine

HRID 279311Notes

Reaction equation

HRID 279311 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:4]=[C:5]([CH:13]=[CH:14][CH:15]=1)[C:6]([NH:8][CH2:9][C:10]([OH:12])=O)=[O:7].CCN=C=NCCCN(C)C.O.ON1C2C=CC=CC=2N=N1.[C:40]([O:44][C:45]([N:47]1[CH2:52][CH2:51][CH:50]([CH2:53][NH2:54])[CH2:49][CH2:48]1)=[O:46])([CH3:43])([CH3:42])[CH3:41]>C(Cl)Cl.O.CCN(CC)CC>[C:40]([O:44][C:45]([N:47]1[CH2:52][CH2:51][CH:50]([CH2:53][NH:54][C:10](=[O:12])[CH2:9][NH:8][C:6](=[O:7])[C:5]2[CH:13]=[CH:14][CH:15]=[C:3]([C:2]([F:1])([F:17])[F:16])[CH:4]=2)[CH2:49][CH2:48]1)=[O:46])([CH3:43])([CH3:42])[CH3:41]

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 7368171-Boc-4-(aminomethyl)piperidineHCID 2777432((3-(Trifluoromethyl)benzoyl)amino)acetic acidHCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 184261501-(tert-butoxycarbonyl)-4-[[N-(3-(trifluoromethyl)benzoyl)glycyl]aminomethyl]piperidineYield 85%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
25 °C

Procedure

N-{3-(Trifluoromethyl)benzoyl}glycine (4.22 g, 17.0 mmol), EDCI (4.25 g, 22.1 mmol), 1-hydroxybenzotriazole hydrate (2.99 g, 22.1 mmol) and Et3N (1.72 g) were added to a solution of 1-(tert-butoxycarbonyl)-4-(aminomethyl)piperidine (4.03 g) in dry CH2Cl2 (200 mL). The reaction mixture was stirred at 25° C. for 20 h. H2O (100 mL) was added to the reaction mixture and the mixture was extracted with CH2Cl2 (2×50 mL). The combined extracts were washed with H2O (2×50 mL), brine (50 mL) and dried (MgSO4). The solvent was removed under reduced pressure to afford an yellow oil which was purified by column chromatography (SiO2, 70% EtOAc-hexane) to give 1-(tert-butoxycarbonyl)-4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine as a white solid (6.39 g, 85%): 1H-NMR (CDCl3, 300 MHz) δ1.4 (s, 9H), 1.0-1.8 (m, 5H), 2.6-2.8 (m, 2H), 3.15-3.3 (m, 2H), 4.0-4.3 (m, 4H), 6.6-6.7 (m, 1H), 7.64 (s, 1H), 7.60 (dd, 1H, J=7.2, 7,2 Hz), 7.79 (d, 1H, J=7,2 Hz), 8.0 (d, 1H, J=7.2 Hz), 8.11 (s, 1H); The purity was determined by RPLc/MS (97); ESI/MS m/e 444.3 (M++H, C21H28F3N3O4).

Workup

  1. extractionthe mixture was extracted with CH2Cl2 (2×50 mL)
  2. washThe combined extracts were washed with H2O (2×50 mL), brine (50 mL)
  3. dry with materialdried (MgSO4)
  4. customThe solvent was removed under reduced pressure
  5. customto afford an yellow oil which
  6. customwas purified by column chromatography (SiO2, 70% EtOAc-hexane)

Sources & evidence

ORD record
ord-537726c383824676b67e2d9257ae27d5
Source dataset
uspto-grants-2002_03
Patent number
US06362177B1

Reaction notes

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