Water → HCID 11774368, compound

HRID 2076436Notes

Reaction equation

HRID 2076436 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:14]=[CH:13][C:9]([C:10](O)=[O:11])=[CH:8][CH:7]=1)=O.Cl.[NH2:31][OH:32].[OH2:33].CCN(CC)CC>O=S(Cl)Cl.CN(C=O)C.C1COCC1>[F:1][C:2]([F:29])([C:15]1[CH:16]=[C:17]2[C:22]([C:21]([CH3:26])([CH3:25])[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]=[CH:8][C:9]([C:10]([NH:31][OH:32])=[O:11])=[CH:13][CH:14]=1)=[O:33]

Participants

8

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 23075279HCID 23075279, compound

Product 1

HCID 11774368HCID 11774368, compoundYield 33.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolventHCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

4-[2,2-Difluoro-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-acetylamino]-benzoic acid 18 (170 mg, 0.425 mmol) was dissolved in SOCl2 (2.4 mL) and two drops of DMF were added at 0° C. The mixture was stirred at 0° C. for 1 h and evaporated and the crude product was dissolved in CH2Cl2 (5 mL). B) Hydroxylamine hydrochloride (1.38 g, 20 mmol) was dissolved in THF (17.2 mL) and water (3.45 mL) and Et3N (3.45 mL) at 0° C., the mixture was stirred at 0° C. for 1 h. A was added in B at 0° C. and this mixture was stirred at 0° C. for 10 min and at RT for 17.75 h. The mixture was evaporated and water was added (50 ml) before to be extracted with CH2Cl2 (3×50 mL). The organic layer was washed with brine (2×20 mL) and dried with MgSO4, filtered and evaporated. The crude product was purified by column chromatography using as eluent cyclohexane:AcOEt=99:1. 4-(2,2-Difluoro-2-(1,2,3,4-tetrahydro-1,1,4,4-tetramethylnaphthalen-7-yl)acetamido)-N-hydroxybenzamide EHT 9299 was obtained (58.3 mg, 33.4% yield) as a pink solid.

Workup

  1. customevaporated
  2. dissolutionthe crude product was dissolved in CH2Cl2 (5 mL)
  3. additionA was added in B at 0° C.
  4. stirringthis mixture was stirred at 0° C. for 10 min and at RT for 17.75 h
  5. customThe mixture was evaporated
  6. additionwater was added (50 ml) before
  7. extractionto be extracted with CH2Cl2 (3×50 mL)
  8. washThe organic layer was washed with brine (2×20 mL)
  9. dry with materialdried with MgSO4
  10. filtrationfiltered
  11. customevaporated
  12. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-c8b8f0b61c464c33be4820be9fc033ac
Source dataset
uspto-grants-2011_04
Patent number
US07923579B2

Reaction notes

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