Potassium Hydroxide → HCID 57467212, compound

HRID 2177080Notes

Reaction equation

HRID 2177080 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][CH:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12]([OH:18])=[CH:13][CH:14]=2)[CH:9]1[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=1)([CH3:4])([CH3:3])[CH3:2].C(OC(=O)NC1CCC2C(=CC(O)=CC=2)C1CC1C=CC(Cl)=C(Cl)C=1)(C)(C)C.[OH-].[K+].Cl[C:59]([F:69])([F:68])C(C1C=CC=CC=1)=O>C(#N)C.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:27])[NH:7][CH:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12]([O:18][CH:59]([F:69])[F:68])=[CH:13][CH:14]=2)[CH:9]1[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 14797Potassium HydroxideHCID 2382962-Chloro-2,2-difluoroacetophenoneHCID 57467203HCID 57467203, compoundHCID 59547800HCID 59547800, compound

Product 1

HCID 57467212HCID 57467212, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Tert-butyl[1-(4-chlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (180 mg, 0.464 mmol, prepared analogously to tert-butyl[1-(3,4-dichlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate, cf. Example 34.2 and potassium hydroxide (1.4 g, 25 mmol) were suspended in acetonitrile (4 mL). After stirring the two phase system for 45 min at room temperature the reaction mixture was cooled to −15° C. and a solution of 2-chloro-2,2-difluoro-1-phenylethanone (442 mg, 2.32 mmol) in acetonitrile (1 mL) was added dropwise over 30 min. The reaction mixture was warmed to room temperature and then heated at 80° C. for 2 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined extracts were dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash chromatography (dichloromethane, silica gel). Yield: 30 mg (0.069 mmol, 15%).

Workup

  1. temperaturewas cooled to −15° C.
  2. temperatureThe reaction mixture was warmed to room temperature
  3. temperatureheated at 80° C. for 2 h
  4. temperatureThe reaction mixture was cooled to room temperature
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialThe combined extracts were dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography (dichloromethane, silica gel)

Sources & evidence

ORD record
ord-0b31baf472ea4d1c80f565788e81e812
Source dataset
uspto-grants-2015_06
Patent number
US09067871B2

Reaction notes

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