Ethyl 3-bromopropionate → Ethyl 3-[9-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]propanoate

HRID 1514244Notes

Reaction equation

Cl.[Cl:2][C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[C:28]4[O:27][CH2:26][CH2:25][NH:24][CH2:23][C:22]=4[CH:21]=[CH:20][CH:19]=3)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11].C(N(CC)C(C)C)(C)C.Br[CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42]>C(#N)C>[Cl:2][C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[C:28]4[O:27][CH2:26][CH2:25][N:24]([CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:23][C:22]=4[CH:21]=[CH:20][CH:19]=3)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 9-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine hydrochloride (Example 31) (260 mg, 0.62 mmol) in acetonitrile (15 ml) was added N,N-diisopropylethylamine (0.214 ml, 1.23 mmol) followed by ethyl 3-bromopropanoate (0.158 ml, 1.231 mmol). The reaction mixture was heated at 80° C. overnight. A further 1 equiv. of N,N-diisopropylethylamine and ethyl 3-bromopropanoate were added and heating continued overnight. The reaction mixture was cooled and evaporated. Purification of the residue by column chromatography, eluting with 50-65% ethyl acetate in cyclohexane to give the title compound as a yellow oil (80 mg).

Workup

temperatureheating continued overnight
temperatureThe reaction mixture was cooled
customevaporated
customPurification of the residue by column chromatography
washeluting with 50-65% ethyl acetate in cyclohexane

Sources & evidence

ORD record: ord-baa0eddfe3ee4b38a9fc3811fc4130c5
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08222245B2

Reaction notes

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