2,6-Dichlorobenzoxazole → 2-acetamido-N-tert-butyl-2-(1-(6-chlorobenzo[d]oxazol-2-yl)piperidin-4-yl)hex-5-enamide

HRID 579559Notes

Reaction equation

HRID 579559 reaction equation
CCN(C(C)C)C(C)C.Cl.[C:11]([NH:15][C:16](=[O:32])[C:17]([NH:28][C:29](=[O:31])[CH3:30])([CH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)[CH2:18][CH2:19][CH:20]=[CH2:21])([CH3:14])([CH3:13])[CH3:12].Cl[C:34]1[O:35][C:36]2[CH:42]=[C:41]([Cl:43])[CH:40]=[CH:39][C:37]=2[N:38]=1>CC(N(C)C)=O.C(OCC)C>[C:29]([NH:28][C:17]([CH:22]1[CH2:27][CH2:26][N:25]([C:34]2[O:35][C:36]3[CH:42]=[C:41]([Cl:43])[CH:40]=[CH:39][C:37]=3[N:38]=2)[CH2:24][CH2:23]1)([CH2:18][CH2:19][CH:20]=[CH2:21])[C:16]([NH:15][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:32])(=[O:31])[CH3:30]

Participants

6

Reactant 3

HCID 771752,6-DichlorobenzoxazoleHCID 81531DiisopropylethylamineHCID 668335742-Acetylamino-2-piperidin-4-yl-hex-5-enoic acid tert-butylamide hydrochloride

Product 1

HCID 668329552-acetamido-N-tert-butyl-2-(1-(6-chlorobenzo[d]oxazol-2-yl)piperidin-4-yl)hex-5-enamideYield 72%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
95 °C

Procedure

Hunigs base (2.5 mL) was added to a stirred suspension of 2-acetylamino-2-piperidin-4-yl-hex-5-enoic acid tert-butylamide hydrochloride (250 mg, 0.73 mmol) and 2,6-dichlorobenzoxazole (172 mg, 0.91 mmol) in anhydrous dimethylacetamide (5 mL). The reaction was stirred at 95° C. overnight under an atmosphere of nitrogen. After heating over night, the reaction mixture was cooled to room temperature and then diluted with diethyl ether. The organic layer was washed with saturated aqueous sodium chloride (3×), dried over MgSO4, filtered and concentrated. The crude product was purified by flash column chromatography (silica gel, 20-80% ethyl acetate in heptane) to give 2-acetamido-N-tert-butyl-2-(1-(6-chlorobenzo[d]oxazol-2-yl)piperidin-4-yl)hex-5-enamide as an off-white solid (240 mg, 72%). 1H NMR (CDCl3, 300 MHz) δ 7.24 (d, J=2 Hz, 1H), 7.21 (d, J=8.5 Hz, 1H), 7.12 (dd, J1=8.5 Hz, J2=2 Hz, 1H), 7.02 (s, NH, 1H), 5.79 (m, 1H), 5.50 (s, NH, 1H), 4.98 (m, 2H), 4.34 (m, 2H), 3.00 (m, 3H), 2.49 (tt, J1=12.5 Hz, J2=3 Hz, 1H), 2.10-1.96 (m, 1H), 2.03 (s, 3H), 1.74-1.93 (m, 3H), 1.49 (m, 1H), 1.33 (s, 9H), 1.18-1.28 (m, 2H).

Workup

  1. temperatureAfter heating over night
  2. temperaturethe reaction mixture was cooled to room temperature
  3. washThe organic layer was washed with saturated aqueous sodium chloride (3×)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash column chromatography (silica gel, 20-80% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-d1c2b32f74ab4fec83f83e8af3e38b29
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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