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

HRID 1514248
Notes
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Reaction equation

HRID 1514248 reaction equation
Cl.[CH3:2][CH:3]([O:5][C:6]1[CH:13]=[CH:12][C:11]([C:14]2[O:18][N:17]=[C:16]([C:19]3[C:29]4[O:28][CH2:27][CH2:26][NH:25][CH2:24][C:23]=4[CH:22]=[CH:21][CH:20]=3)[N:15]=2)=[CH:10][C:7]=1[C:8]#[N:9])[CH3:4].C(N(CC)C(C)C)(C)C.Br[CH2:40][CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43]>C(#N)C>[C:8]([C:7]1[CH:10]=[C:11]([C:14]2[O:18][N:17]=[C:16]([C:19]3[C:29]4[O:28][CH2:27][CH2:26][N:25]([CH2:40][CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH2:24][C:23]=4[CH:22]=[CH:21][CH:20]=3)[N:15]=2)[CH:12]=[CH:13][C:6]=1[O:5][CH:3]([CH3:2])[CH3:4])#[N:9]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 68320Ethyl 3-bromopropionate2×HCID 81531Diisopropylethylamine2×HCID 68468994HCID 68468994, compound

Product 1

HCID 59403543Ethyl 3-[9-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]propanoateYield 38.5%

Reagents, catalysts & solvents 1

HCID 6342
Acetonitrile
Solvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1,4-benzoxazepin-9-yl)-1,2,4-oxadiazol-5-yl]benzonitrile hydrochloride (Example 32) (90 mg, 0.218 mmol) in acetonitrile (10 ml) was added N,N-diisopropylethylamine (0.076 ml, 0.436 mmol) followed by ethyl 3-bromopropanoate (0.056 ml, 0.436 mmol). The reaction mixture was heated at 80° C. overnight. A further 1 equivalent 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 on silica, eluting with 60-70% ethyl acetate in cyclohexane to give the title compound as a brown oil (40 mg).

Workup

  1. temperatureheating continued overnight
  2. temperatureThe reaction mixture was cooled
  3. customevaporated
  4. customPurification of the residue by column chromatography on silica
  5. washeluting with 60-70% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-fbcbcb55f29b4cdf88f62918045e96bc
Source dataset
uspto-grants-2012_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08222245B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes