Triethylamine → (+/-)-cis-1-(2-Azido-cyclohexyl)-4-(4-chlorobenzyl)-piperidine

HRID 1744835

Reaction equation

HRID 1744835 reaction equation
[N:1]([C@@H:4]1[CH2:9][CH2:8][CH2:7][CH2:6][C@H:5]1OS(C1C=CC([N+]([O-])=O)=CC=1)(=O)=O)=[N+:2]=[N-:3].[Cl:23][C:24]1[CH:36]=[CH:35][C:27]([CH2:28][CH:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[CH:26][CH:25]=1.CCN(CC)CC>CC#N>[N:1]([C@H:4]1[CH2:9][CH2:8][CH2:7][CH2:6][C@H:5]1[N:32]1[CH2:33][CH2:34][CH:29]([CH2:28][C:27]2[CH:26]=[CH:25][C:24]([Cl:23])=[CH:36][CH:35]=2)[CH2:30][CH2:31]1)=[N+:2]=[N-:3]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 37327804-(4-Chlorobenzyl)piperidineHCID 59122973(+/-)-trans-4-Nitro-benzenesulfonic acid 2-azidocyclohexyl ester2×

Product 1

HCID 23587484(+/-)-cis-1-(2-Azido-cyclohexyl)-4-(4-chlorobenzyl)-piperidineYield 9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A murky solution of (±)-trans-4-nitro-benzenesulfonic acid 2-azido-cyclohexyl ester (1.77 g, 5.41 mmol), 4-(4-chlorobenzyl)-piperidine (1.14 g, 5.43 mmol), and Et3N (0.75 mL, 5.4 mmol) in CH3CN (11.2 mL) was stirred at room temperature for 17 hours, 65° C. for 31 hours, and 80° C. for 5 d, allowed to cool to room temperature, and concentrated. The residue was partitioned between CH2Cl2 and 1 N NaOH, the aqueous phase was extracted with CH2Cl2 and the extracts were dried and concentrated. Chromatography of the residue with 98:1.9:0.1–95:4.75:0.25 CH2Cl2:MeOH:NH4OH to 100% MeOH and subsequent chromatography with 10:1 hexanes:EtOAc to 100% EtOAc followed by 95:5 EtOAc:MeOH gave, in order of elution, starting (±)-trans-4-nitro-benzenesulfonic acid 2-azidocyclohexyl ester (1.2 g, 68%), desired product (155 mg, 9%), and starting 4-(4-chlorobenzyl)-piperidine (810 mg, 71%). Product: 1H NMR δ 1.19–1.81 (m, 12H), 1.92–2.08 (m, 3H), 2.22 (m, 1H), 2.48 (d, J=7.0 Hz, 2H), 3.02 (m, 2H), 4.05 (m, 1H), 7.06 (m, 2H), 7.23 (m, 2H); MS m/z 333.2 (M+H)+.

Workup

  1. concentrationconcentrated
  2. customThe residue was partitioned between CH2Cl2 and 1 N NaOH
  3. extractionthe aqueous phase was extracted with CH2Cl2
  4. customthe extracts were dried
  5. concentrationconcentrated
  6. customMeOH gave, in order of elution

Sources & evidence

ORD record
ord-49f2657337c54df1b58eeb201a42c21b
Source dataset
uspto-grants-2006_03
Patent number
US07019007B2

Linked notes

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