Ethyl 3-bromopropionate → Ethyl 3-[8-(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 1514201Notes

Reaction equation

HRID 1514201 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:27]=[CH:26][C:20]4[CH2:21][NH:22][CH2:23][CH2:24][O:25][C:19]=4[CH:18]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].Br[CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32].CCN(C(C)C)C(C)C>CCOC(C)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:27]=[CH:26][C:20]4[CH2:21][N:22]([CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:23][CH2:24][O:25][C:19]=4[CH:18]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

5

Reactant 3

HCID 68320Ethyl 3-bromopropionate3×HCID 81531Diisopropylethylamine3×HCID 44128821HCID 44128821, compound

Product 1

HCID 59403499Ethyl 3-[8-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]propanoateYield 93.1%

Reagents, catalysts & solvents 1

HCID 22728543Water ethylacetateSolvent

Procedure

A mixture of 8-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine (Example 13) (0.036 g, 0.199 mmol), ethyl 3-bromopropanoate (0.084 g, 0.199 mmol) and DIPEA (0.097 ml, 0.557 mmol) was stirred and heated at 80° C. for 4 hours when a further portion of ethyl 3-bromopropanoate (0.084 g, 0.199 mmol) and DIPEA (0.097 ml, 0.557 mmol) were added and heated overnight when a further portion of ethyl 3-bromopropanoate (0.084 g, 0.199 mmol) and DIPEA (0.097 ml, 0.557 mmol) were added and heated for 3 more hours when all starting material gone. The cooled reaction mixture was diluted with EtOAc/water (30 ml of each) and the organics dried (magnesium sulphate), evaporated and purified by flash chromatography eluting with 1:1 EtOAc/iso-hexane to give the title compound (90 mgs) as a colourless gum. MS (ES) C25H2835ClN3O5 requires 485; found 486 [M+H]+.

Workup

  1. additionwere added
  2. additionwere added
  3. temperatureheated for 3 more hours when all starting material
  4. customThe cooled reaction mixture
  5. dry with materialorganics dried (magnesium sulphate)
  6. customevaporated
  7. custompurified by flash chromatography
  8. washeluting with 1:1 EtOAc/iso-hexane

Sources & evidence

ORD record
ord-5dda47eaaa2b44de8f565195cc9e013a
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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