Potassium Carbonate → 1,1-dimethylethyl 3-[6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]propanoate

HRID 1514188Notes

Reaction equation

HRID 1514188 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[C:27]4[CH2:26][CH2:25][NH:24][CH2:23][CH2:22][C:21]=4[CH:20]=[CH:19][CH:18]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].C(=O)([O-])[O-].[K+].[K+].Br[CH2:35][CH2:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[C:27]4[CH2:26][CH2:25][N:24]([CH2:35][CH2:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:23][CH2:22][C:21]=4[CH:20]=[CH:19][CH:18]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 256128tert-Butyl 3-bromopropionateHCID 441287466-(5-{3-chloro-4-[(1-methyl ethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine

Product 1

HCID 594034501,1-dimethylethyl 3-[6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]propanoateYield 25.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

In a 5 ml microwave reaction vessel was added 6-(5-{3-chloro-4-[(1-methyl ethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine (Free base of Example 8, obtained by standard methods e.g. partitioning between organic and basic aqueous solvents and collecting organic solvent) (70 mg) in DMF (3 ml) to give a brown solution. Then potassium carbonate (101 mg) was added followed by 1,1-dimethylethyl 3-bromopropanoate (38.1 mg, 0.182 mmol). The reaction mixture was heated at 100° C. for 10 minutes. The cooled reaction mixture was diluted with DCM (5 ml) and purified by SCX (washing with methanol and eluting the crude amino ester with methanolic ammonia). Purification by MDAP yielded the amino ester, 1,1-dimethylethyl 3-[6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]propanoate (25 mg, 0.046 mmol, 25.4% yield) isolated as a light yellow oil. MS (ES) C28H3435ClN3O4 requires 511; found 512 [M+H]+.

Workup

  1. customobtained by standard methods e.g.
  2. custompartitioning between organic and basic aqueous solvents
  3. customcollecting organic solvent) (70 mg) in DMF (3 ml)
  4. customto give a brown solution
  5. customThe cooled reaction mixture
  6. custompurified by SCX (
  7. washwashing with methanol
  8. washeluting the crude amino ester with methanolic ammonia)
  9. customPurification by MDAP

Sources & evidence

ORD record
ord-10727254f4f045459d5b06f65937bce0
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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