Water → HCID 11750392, compound

HRID 2076439Notes

Reaction equation

HRID 2076439 reaction equation
[F:1][C:2]([F:29])([C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[C:21]([CH3:26])([CH3:25])[CH2:20][CH2:19][C:18]2([CH3:28])[CH3:27])[C:3]([NH:5][C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9](O)=[O:10])=[O:4].Cl.[NH2:31][OH:32].O.CCN(CC)CC>O=S(Cl)Cl.CN(C=O)C.C1COCC1>[F:29][C:2]([F:1])([C:15]1[CH:16]=[C:17]2[C:22]([C:21]([CH3:25])([CH3:26])[CH2:20][CH2:19][C:18]2([CH3:27])[CH3:28])=[CH:23][CH:24]=1)[C:3]([NH:5][C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([NH:31][OH:32])=[O:10])=[O:4]

Participants

8

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 23075278HCID 23075278, compound

Product 1

HCID 11750392HCID 11750392, compoundYield 10%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolventHCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

3-(2,2-Difluoro-2-(1,2,3,4-tetrahydro-1,1,4,4-tetramethylnaphthalen-6-yl)acetamido)benzoic acid 20 (407 mg, 1.02 mmol) was dissolved in SOCl2 (5.7 mL) and two drops of DMF were added at 0° C. This mixture was stirred at 0° C. for 1 h then evaporated under vacuum and the crude product was dissolved in CH2Cl2 (5 mL). B) Hydroxylamine hydrochloride (3.18 g, 45.7 mmol) was dissolved in THF (41.17 mL) and water (8.25 mL) and Et3N (8.25 mL) at 0° C., the mixture was stirred at 0° C. for 1 h. Solution A) was added at 0° C. via syringe in B) and the mixture was stirred at 0° C. for 10 min and abandoned at RT for 19 h. The mixture was evaporated and the residue obtained was extracted with CH2Cl2 (3×50 mL) and washed with water (50 mL). The organic layer was washed with brine (2×50 mL), dried over MgSO4, filtered and evaporated. The crude product was purified by column chromatography eluent (cyclohexane:EtOAc=98:02). 3-(2,2-Difluoro-2-(1,2,3,4-tetrahydro-1,1,4,4-tetramethylnaphthalen-7-yl)acetamido)-N-hydroxybenzamide EHT 9710 was obtained (40 mg, 10% yield) as an orange solid.

Workup

  1. customthen evaporated under vacuum
  2. dissolutionthe crude product was dissolved in CH2Cl2 (5 mL)
  3. stirringwas stirred at 0° C. for 10 min
  4. waitabandoned at RT for 19 h
  5. customThe mixture was evaporated
  6. customthe residue obtained
  7. extractionwas extracted with CH2Cl2 (3×50 mL)
  8. washwashed with water (50 mL)
  9. washThe organic layer was washed with brine (2×50 mL)
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. customevaporated
  13. customThe crude product was purified by column chromatography eluent (cyclohexane:EtOAc=98:02)

Sources & evidence

ORD record
ord-6775d701c68245cdae7e4300082a128a
Source dataset
uspto-grants-2011_04
Patent number
US07923579B2

Reaction notes

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