Ammonium Chloride → 6-[(4-tert-Butylphenyl)(hydroxy)methyl]-5-(4-fluorophenyl)-7-isopropylspiro[chromen-2,1'-cyclo-butan]-4(3H)-one

HRID 1516719Notes

Reaction equation

HRID 1516719 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:20]([CH:21]=[O:22])=[C:19]([CH:23]([CH3:25])[CH3:24])[CH:18]=[C:17]3[C:9]=2[C:10](=[O:26])[CH2:11][C:12]2([O:16]3)[CH2:15][CH2:14][CH2:13]2)=[CH:4][CH:3]=1.[C:27]([C:31]1[CH:36]=[CH:35][C:34]([Mg]Br)=[CH:33][CH:32]=1)([CH3:30])([CH3:29])[CH3:28].[Cl-].[NH4+]>O1CCCC1.Cl>[C:27]([C:31]1[CH:36]=[CH:35][C:34]([CH:21]([OH:22])[C:20]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[C:9]3[C:17](=[CH:18][C:19]=2[CH:23]([CH3:24])[CH3:25])[O:16][C:12]2([CH2:15][CH2:14][CH2:13]2)[CH2:11][C:10]3=[O:26])=[CH:33][CH:32]=1)([CH3:30])([CH3:29])[CH3:28]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 580030415-(4-Fluorophenyl)-7-isopropyl-4-oxo-3,4-dihydrospiro[chromen-2,1'-cyclobutane]-6-carbaldehydeHCID 178440986HCID 178440986, compound

Product 1

HCID 580029576-[(4-tert-Butylphenyl)(hydroxy)methyl]-5-(4-fluorophenyl)-7-isopropylspiro[chromen-2,1'-cyclo-butan]-4(3H)-one

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Under argon, 0.30 g (0.851 mmol) of 5-(4-fluorophenyl)-7-isopropyl-4-oxo-3,4-dihydrospiro-[chromen-2,1′-cyclobutane]-6-carbaldehyde (Example 51A) is suspended in 6 ml of tetrahydrofuran and cooled to −78° C. 2.54 ml (1.28 mmol) of a freshly prepared 0.5 M solution of [4-(tert-butyl)phenyl]magnesium bromide in tetrahydrofuran are added slowly. The mixture is briefly stirred at −78° C. and then warmed to 0° C. After about 1.5 h, saturated ammonium chloride solution is added and the mixture is diluted with a little 1 N hydrochloric acid and extracted repeatedly with ethyl acetate. The combined organic phases are washed twice with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The crude product is purified a little at a time by preparative HPLC (method 12). This gives 0.239 g (58% of theory) of the title compound.

Workup

  1. temperaturewarmed to 0° C
  2. extractionextracted repeatedly with ethyl acetate
  3. washThe combined organic phases are washed twice with saturated sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product is purified a little at a time by preparative HPLC (method 12)

Sources & evidence

ORD record
ord-ee61105f7a924f59946c402fcf88a2c6
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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