Hydrochloric Acid → HCID 22251420, compound

HRID 1934868Notes

Reaction equation

HRID 1934868 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[OH:9].C([O:12][C:13](=[O:23])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20](O)=[O:21])C.B(O)(O)O.[OH-].[Na+].Cl>C1(C)C=CC=CC=1.C(OCC)(=O)C.O>[Cl:8][C:6]1[CH:5]=[CH:4][C:3]([OH:9])=[C:2]([CH:7]=1)[NH:1][C:20](=[O:21])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][C:13]([OH:23])=[O:12]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 72652-Amino-4-chlorophenolHCID 7628Boric AcidHCID 14798Sodium HydroxideHCID 842048-Ethoxy-8-oxooctanoic acid

Product 1

HCID 22251420HCID 22251420, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

8-(5-chloro-2-hydroxyanilino)-8-oxooctanoic acid was prepared as follows. A suspension of 2-amino-4-chlorophenol (17.88 g, 124.5 mmol), 8-ethoxy-8-oxooctanoic acid (25.19 g, 124.5 mmol), boric acid (0.385 g, 6.23 mmol) in 150 mL of dried toluene was heated at reflux (110° C.) under nitrogen for 4 hours during which water (2.5 mL) produced in the reaction was removed by azeotropic distillation in a Dean-Stark separation unit. The reaction was observed by thin layer chromatography on silica gel (Eluant: ethylacetate:heptane 1:1). The reaction mixture was cooled in a water bath to room temperature. 2N aqueous solution of sodium hydroxide (125 mL, 250 mmol) was added to the mixture. The mixture was heated at reflux for 4 hours. The reaction mixture was cooled in a water bath to room temperature. The mixture was then diluted with ethyl acetate (300 mL) and water (150 mL). The aqueous layer was washed with two portions of ethyl acetate (250 mL). After careful separation, the aqueous layer was chilled and acidified with a 10% (by weight) solution of hydrochloric acid (86.20 mL, 250 mmol) to yield a solid which was filtered, washed with hexane, and dried under vacuum. Trituration with dichloromethane yielded the desired acid (21.75 g, 57%) as an off-white solid. HPLC (Column: Higgins Kromasil 100 C18, water/acetonitile/acetic acid: 950/50/1, 3 mL/min, 220 nm) showed one single peak. Rt was 5.38 minutes.

Workup

  1. temperaturewas heated
  2. customproduced in the reaction
  3. customwas removed by azeotropic distillation in a Dean-Stark separation unit
  4. temperatureThe mixture was heated
  5. temperatureat reflux for 4 hours
  6. temperatureThe reaction mixture was cooled in a water bath to room temperature
  7. washThe aqueous layer was washed with two portions of ethyl acetate (250 mL)
  8. customAfter careful separation
  9. temperaturethe aqueous layer was chilled
  10. customto yield a solid which
  11. filtrationwas filtered
  12. washwashed with hexane
  13. customdried under vacuum

Sources & evidence

ORD record
ord-f9352b9fc8e947698e2b7a2c43422f67
Source dataset
uspto-grants-2002_05
Patent number
US06384278B1

Reaction notes

Loading…