4-Amino-1-Boc-piperidine → HCID 11568879, compound

HRID 2422088Notes

Reaction equation

HRID 2422088 reaction equation
[C:1]([N:5]1[C:9](=[O:10])[C:8](Cl)=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:6]1(=[O:19])=[O:18])([CH3:4])([CH3:3])[CH3:2].[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30]([NH2:33])[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21]>CC#N>[C:1]([N:5]1[C:9](=[O:10])[C:8]([NH:33][CH:30]2[CH2:29][CH2:28][N:27]([C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])[CH2:32][CH2:31]2)=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:6]1(=[O:19])=[O:18])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 12682914-Amino-1-Boc-piperidine2×HCID 672426272-tert-Butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide

Product 1

HCID 11568879HCID 11568879, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 2-tert-butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide (2.000 g, 6.672 mmol), tert-butyl-4-aminopiperidine-1-carboxylate (1.336 g, 6.672 mmol) and TEA (0.933 ml, 6.672 mmol) in MeCN (20 ml) was heated in a microwave reactor at 120° C. for 40 mins and 130° C. for 30 mins. tert-Butyl-4-aminopiperidine-1-carboxylate (0.267 mg, 1.334 mmol) and TEA (0.187 ml, 1.334 mmol) was added and the resulting mixture was heated in a microwave reactor for at 120° C. for 20 mins. The reaction mixture was evaporated to dryness and the residue was purified by silica gel column chromatography (Horizons Biotage) eluting with 10% petroleum ether 40-60° C. in DCM then 0-20% EtOAc in DCM to give the title compound (2.228 g, 72%) as a solid. 1H NMR (500 MHz, CDCl3): δ 7.54-7.50 (m, 2H), 7.50-7.44 (m, 3H), 5.17 (d, 1H), 3.88 (bs, 2H), 3.08-3.00 (m, 1H), 2.32 (dt, 2H), 1.74 (s, 9H), 1.68-1.60 (m, 2H), 1.42 (s, 9H), 1.30-1.17 (m, 2H); 13C NMR (125 MHz, CDCl3): δ 159.8, 154.7, 134.1, 131.9, 130.2, 128.9, 125.3, 107.3, 80.1, 61.9, 50.4, 42.4, 32.4, 28.6, 27.9; Mass Spectrum M+H+ 464.

Workup

  1. temperaturethe resulting mixture was heated in a microwave reactor for at 120° C. for 20 mins
  2. customThe reaction mixture was evaporated to dryness
  3. customthe residue was purified by silica gel column chromatography (Horizons Biotage)
  4. washeluting with 10% petroleum ether 40-60° C. in DCM

Sources & evidence

ORD record
ord-c3da3c71230b4cf9b094cfb12ae5a72a
Source dataset
uspto-grants-2011_06
Patent number
US07960380B2

Reaction notes

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