Triethylamine → 4-(Benzothiazol-2-ylamino)-piperidine-1-carboxylic acid ethyl ester

HRID 1990794Notes

Reaction equation

HRID 1990794 reaction equation
Cl[C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[NH2:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:14][CH2:13]1.C(N(CC)CC)C>ClCCl>[CH2:21]([O:20][C:18]([N:15]1[CH2:14][CH2:13][CH:12]([NH:11][C:2]2[S:3][C:4]3[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=3[N:6]=2)[CH2:17][CH2:16]1)=[O:19])[CH3:22]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 119872-ChlorobenzothiazoleHCID 100867Ethyl 4-amino-1-piperidinecarboxylate

Product 1

HCID 157251204-(Benzothiazol-2-ylamino)-piperidine-1-carboxylic acid ethyl esterYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
180 °C

Procedure

A mixture of 2-chloro-benzothiazole (2.00 g, 12.0 mmol, 1.0 equiv), ethyl 4-amino-1-piperidine carboxylate (2.44 g, 14.0 mmol, 1.2 equiv) and triethylamine (1.79 g, 18.0 mmol, 1.5 equiv) was heated by microwave irradiation to 180° C. for 5 min. To the crude reaction mixture was added dichloromethane (10 mL) and the suspension quickly poured onto tert-butyl methylether (200 mL). The hydrochloric salts of remaining ethyl 4-amino-1-piperidine carboxylate and triethylamine precipitated out and were removed by filtration. The filtrate was evaporated to dryness and the residue purified with column chromatography on silica eluting with dichloromethane/methanol (95:5) to yield 2.7 g (75%) of the title compound as a white solid. 1H NMR (300 MHz, DMSO): δ 1.19 (t, J=7.1 Hz, 3H), 1.31-1.44 (m, 2H), 1.96-2.01 (m, 2H), 2.98-3.06 (m, 2H), 3.88-3.98 (m, 3H), 4.04 (q, J=7.1 Hz, 2H), 7.01 (t, J=7.4 Hz, 1H), 7.21 (t, J=7.8 Hz, 1H), 7.39 (d, J=7.4 Hz, 1H), 7.65 (d, J=7.8 Hz, 1H), 8.01 (d, J=7.3 Hz, 1H). MS (ISP): 306.0 [M+H]+.

Workup

  1. customTo the crude reaction mixture
  2. additionthe suspension quickly poured onto tert-butyl methylether (200 mL)
  3. customThe hydrochloric salts of remaining ethyl 4-amino-1-piperidine carboxylate and triethylamine precipitated out
  4. customwere removed by filtration
  5. customThe filtrate was evaporated to dryness
  6. customthe residue purified with column chromatography on silica eluting with dichloromethane/methanol (95:5)

Sources & evidence

ORD record
ord-fa8768dde55346768bef23b513463827
Source dataset
uspto-grants-2010_01
Patent number
US07645753B2

Reaction notes

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