5,6,7,8-Tetrahydro-2-naphthol → HCID 72545673, compound

HRID 1427816Notes

Reaction equation

HRID 1427816 reaction equation
[CH:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][C:2]=1[OH:11].[H-].[Na+].[Cl:14][C:15]1[C:16]([F:29])=[CH:17][C:18]([F:28])=[C:19]([CH:27]=1)[C:20]([NH:22][S:23]([CH3:26])(=[O:25])=[O:24])=[O:21].[NH4+].[Cl-]>CN(C=O)C>[Cl:14][C:15]1[C:16]([O:11][C:2]2[CH:3]=[CH:4][C:5]3[CH2:6][CH2:7][CH2:8][CH2:9][C:10]=3[CH:1]=2)=[CH:17][C:18]([F:28])=[C:19]([CH:27]=1)[C:20]([NH:22][S:23]([CH3:26])(=[O:24])=[O:25])=[O:21].[Cl:14][C:15]1[C:16]([F:29])=[CH:17][C:18]([O:11][C:2]2[CH:3]=[CH:4][C:5]3[CH2:6][CH2:7][CH2:8][CH2:9][C:10]=3[CH:1]=2)=[C:19]([CH:27]=1)[C:20]([NH:22][S:23]([CH3:26])(=[O:25])=[O:24])=[O:21]

Participants

7

Reactant 4

HCID 143055,6,7,8-Tetrahydro-2-naphtholHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 580424175-chloro-2,4-difluoro-N-(methylsulfonyl)benzamide

Product 2

HCID 72545673HCID 72545673, compoundYield 30%HCID 86702842HCID 86702842, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5,6,7,8-tetrahydronaphthalen-2-ol (66 mg, 0.44 mmol) in DMF (3 mL) was added NaH (19 mg, 0.48 mmol). After being stirred at room temperature for 0.5 h, 5-chloro-2,4-difluoro-N-(methylsulfonyl)benzamide (100 mg, 0.37 mmol) was added and the mixture was stirred at room temperature for 16 h. Sat. NH4Cl (10 mL) was added to quench the reaction and the resulting mixture was extracted with ethyl acetate (10 mL×3). The combined organic layer was dried over NaSO4 and concentrated in vacuo. The residue was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to afford 5-chloro-2-fluoro-N-(methylsulfonyl)-4-(5,6,7,8-tetrahydronaphthalen-2-yloxy)benzamide (44 mg, 30% yield) and 5-chloro-4-fluoro-N-(methylsulfonyl)-2-(5,6,7,8-tetrahydronaphthalen-2-yloxy)-benzamide (21 mg, 14% yield).

Workup

  1. stirringthe mixture was stirred at room temperature for 16 h
  2. customto quench
  3. customthe reaction
  4. extractionthe resulting mixture was extracted with ethyl acetate (10 mL×3)
  5. dry with materialThe combined organic layer was dried over NaSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min)

Sources & evidence

ORD record
ord-0105205f98154cb88fae92c0ec7be40d
Source dataset
uspto-grants-2015_01
Patent number
US08933236B2

Reaction notes

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