Ethyl 4-bromobutyrate → Ethyl 4-[8-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]butanoate

HRID 1514202Notes

Reaction equation

HRID 1514202 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].CCN(C(C)C)C(C)C.Br[CH2:38][CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42]>C(#N)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]([CH2:38][CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[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

6

Reactant 3

HCID 76300Ethyl 4-bromobutyrateHCID 81531DiisopropylethylamineHCID 44128821HCID 44128821, compound

Product 1

HCID 59403500Ethyl 4-[8-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]butanoateYield 70.7%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
70 °C

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) (0.127 g, 0.3 mmol), DIPEA (0.052 ml, 0.300 mmol) and ethyl 4-bromobutanoate (0.059 g, 0.300 mmol) in acetonitrile (5 ml) was stirred and heated at 70° C. for 15 hours. The cooled reaction mixture was diluted and dissolved in 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 (106 mgs) as a colourless gum. MS (ES) C28H3835ClN3O5 requires 499; found 500 [M+H]+.

Workup

  1. customThe cooled reaction mixture
  2. additionwas diluted
  3. dry with materialorganics dried (magnesium sulphate)
  4. customevaporated
  5. custompurified by flash chromatography
  6. washeluting with 1:1 EtOAc/iso-hexane

Sources & evidence

ORD record
ord-7238874bbec44d06af91393f10c09ff6
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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