Acetic Acid → HCID 118179072, compound

HRID 1050733Notes

Reaction equation

HRID 1050733 reaction equation
[CH2:1]([O:3][C:4](=[O:34])[CH2:5][CH2:6][CH2:7][CH2:8][N:9]([CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[O:32]C)[CH:10]1[CH2:19][CH2:18][CH2:17][C:16]2[CH:15]=[C:14]([C:20]([O:22][CH3:23])=[O:21])[CH:13]=[CH:12][C:11]1=2)[CH3:2].Br.[C:36](O)(=O)C>>[CH2:1]([O:3][C:4](=[O:34])[CH2:5][CH2:6][CH2:7][CH2:8][N:9]([CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[OH:32])[CH:10]1[CH2:19][CH2:18][CH2:17][C:16]2[CH:15]=[C:14]([C:20]([O:22][CH2:23][CH3:36])=[O:21])[CH:13]=[CH:12][C:11]1=2)[CH3:2]

Participants

4

Reactant 3

HCID 176Acetic AcidHCID 260Hydrogen Bromide2×HCID 118179066HCID 118179066, compound

Product 1

HCID 118179072HCID 118179072, compound

Conditions

Temperature
135 °C

Procedure

8.7 g (18.6 mmol) of the compound from Example 2A were stirred in 90 ml of a 33% strength solution of hydrogen bromide in glacial acetic acid under reflux overnight. After addition of another 90 ml of hydrogen bromide solution, the mixture was stirred at a bath temperature of 135° C. for a further night. The mixture was then concentrated under reduced pressure, another 40 ml of the solution of hydrogen bromide in glacial acetic acid were added to the residue and the mixture was stirred at a bath temperature of 110° C. for another night. The mixture was then once more concentrated to dryness. The residue, which comprised 77% of the dicarboxylic acid compound 5-{(4-carboxybutyl) [2-(2-hydroxyphenyl)ethyl]amino}-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid [LC-MS (Method 2): Rt=0.64 min; MS (ESIpos): m/z=412 [M+H]+], was subjected to incipient dissolution in 190 ml of ethanol, and 1.65 ml of thionyl chloride were added dropwise. The mixture was stirred at 70° C. overnight and then concentrated under reduced pressure. The residue (about 13 g) was taken up in ethyl acetate and washed twice with dilute aqueous sodium carbonate solution. The organic phase was dried over sodium sulphate and concentrated. The crude product (8.8 g) was purified by flash chromatography on silica gel using the mobile phase cyclohexane/ethyl acetate 5:1.

Workup

  1. temperatureunder reflux overnight
  2. concentrationThe mixture was then concentrated under reduced pressure
  3. additionanother 40 ml of the solution of hydrogen bromide in glacial acetic acid were added to the residue
  4. stirringthe mixture was stirred at a bath temperature of 110° C. for another night
  5. concentrationThe mixture was then once more concentrated to dryness
  6. dissolutionwas subjected to incipient dissolution in 190 ml of ethanol
  7. addition1.65 ml of thionyl chloride were added dropwise
  8. stirringThe mixture was stirred at 70° C. overnight
  9. concentrationconcentrated under reduced pressure
  10. washwashed twice with dilute aqueous sodium carbonate solution
  11. dry with materialThe organic phase was dried over sodium sulphate
  12. concentrationconcentrated
  13. customThe crude product (8.8 g) was purified by flash chromatography on silica gel using the mobile phase cyclohexane/ethyl acetate 5:1

Sources & evidence

ORD record
ord-88ec7b50bd01474db0433f8ad72210ac
Source dataset
uspto-grants-2016_07
Patent number
US09387203B2

Reaction notes

Loading…