2,3-Difluorobenzoyl chloride → HCID 58923398, compound

HRID 1951046Notes

Reaction equation

HRID 1951046 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[N:5]1([C:11]2[CH:12]=[C:13]([OH:18])[CH:14]=[C:15]([OH:17])[CH:16]=2)[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.[F:19][C:20]1[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:21]=1[C:22](Cl)=[O:23]>[N+](C1C=CC=CC=1)([O-])=O>[F:19][C:20]1[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:21]=1[C:22]([C:14]1[C:13]([OH:18])=[CH:12][C:11]([N:5]2[CH2:10][CH2:9][O:8][CH2:7][CH2:6]2)=[CH:16][C:15]=1[OH:17])=[O:23]

Participants

5

Reactant 3

HCID 5195492,3-Difluorobenzoyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 58923367HCID 58923367, compound

Product 1

HCID 58923398HCID 58923398, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 7416NitrobenzeneSolvent2×

Conditions

Temperature
110 °C

Procedure

Aluminum chloride (905 mg, 6.79 mmol) was added to a solution of 5-morpholin-4-yl-benzene-1,3-diol in nitrobenzene (8 mL), and the mixture was heated to 110° C. A solution of 2,3-difluorobenzoyl chloride in nitrobenzene was added slowly, and the mixture was heated at 100° C. for 12 h. The majority of the nitrobenzene was removed via short-path vacuum distillation. The black residue was dissolved in water/EtOAc (1:1, 20 mL). The aqueous component was extracted with EtOAc (3×40 mL), and the combined extracts were dried (MgSO4) and filtered through a ¾-inch silica gel plug. The filtrate was concentrated and purified via Biotage chromatography (100% hexanes to 30% EtOAc/hexanes) to yield 196 mg (22%) of (2,3-difluorophenyl)-(2,6-dihydroxy-4-morpholin-4-yl-phenyl)methanone. 1H NMR (CDCl3, 400 MHz) δ: 7.30-7.10 (comp., 3H), 5.85 (s, 2H), 3.85-3.75 (m, 4H), 3.42-3.38 (m, 4H).

Workup

  1. temperaturethe mixture was heated at 100° C. for 12 h
  2. customThe majority of the nitrobenzene was removed via short-path vacuum distillation
  3. dissolutionThe black residue was dissolved in water/EtOAc (1:1, 20 mL)
  4. extractionThe aqueous component was extracted with EtOAc (3×40 mL)
  5. dry with materialthe combined extracts were dried (MgSO4)
  6. filtrationfiltered through a ¾-inch silica gel plug
  7. concentrationThe filtrate was concentrated
  8. custompurified via Biotage chromatography (100% hexanes to 30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d8de61cd5d284fc0bf4b47dfa15ad70b
Source dataset
uspto-grants-2013_03
Patent number
US08404681B2

Reaction notes

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