Ammonium Chloride → 4-[(4E)-3-{3,5-difluoro-4-[(triisopropylsilyl)oxy]benzyl}-5-(2-hydroxyphenyl)pent-4-en-1-yl]benzonitrile

HRID 1921895Notes

Reaction equation

HRID 1921895 reaction equation
C([Li])CCC.[Br-].[OH:7][C:8]1[CH:33]=[CH:32][CH:31]=[CH:30][C:9]=1[CH2:10][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[F:34][C:35]1[CH:36]=[C:37]([CH:52]=[C:53]([F:66])[C:54]=1[O:55][Si:56]([CH:63]([CH3:65])[CH3:64])([CH:60]([CH3:62])[CH3:61])[CH:57]([CH3:59])[CH3:58])[CH2:38][CH:39]([CH:50]=O)[CH2:40][CH2:41][C:42]1[CH:49]=[CH:48][C:45]([C:46]#[N:47])=[CH:44][CH:43]=1.[Cl-].[NH4+]>CCCCCC.C1COCC1>[F:34][C:35]1[CH:36]=[C:37]([CH:52]=[C:53]([F:66])[C:54]=1[O:55][Si:56]([CH:57]([CH3:59])[CH3:58])([CH:60]([CH3:62])[CH3:61])[CH:63]([CH3:65])[CH3:64])[CH2:38][CH:39](/[CH:50]=[CH:10]/[C:9]1[CH:30]=[CH:31][CH:32]=[CH:33][C:8]=1[OH:7])[CH2:40][CH2:41][C:42]1[CH:49]=[CH:48][C:45]([C:46]#[N:47])=[CH:44][CH:43]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 2724142(2-Hydroxybenzyl)triphenylphosphonium bromideHCID 579719344-[3-(3,5-Difluoro-4-triisopropylsilanyloxybenzyl)-4-oxobutyl]benzonitrileHCID 178418339Butyllithium

Product 1

HCID 579719094-[(4E)-3-{3,5-difluoro-4-[(triisopropylsilyl)oxy]benzyl}-5-(2-hydroxyphenyl)pent-4-en-1-yl]benzonitrile

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

1.82 ml (2.91 mmol) of a 1.6 M solution of n-butyllithium in hexane are slowly added to a solution of 579 mg (1.25 mmol) of (2-hydroxybenzyl)triphenylphosphonium bromide in 11.5 ml of THF at 0° C. Then, at this temperature, 490 mg (1.04 mmol) of 4-[3-(3,5-difluoro-4-triisopropylsilanyloxybenzyl)-4-oxobutyl]benzonitrile are slowly metered in. The reaction solution is stirred at 0° C. for 2 h and then mixed with 100 ml of saturated ammonium chloride solution and extracted with diethyl ether. The combined organic phases are washed with saturated sodium chloride solution and dried over sodium sulfate. After filtration, the solvent is concentrated to dryness. The resulting crude product is purified by flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 10:1). 379.7 mg (54% of theory) of a colorless solid are obtained.

Workup

  1. extractionextracted with diethyl ether
  2. washThe combined organic phases are washed with saturated sodium chloride solution
  3. dry with materialdried over sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe solvent is concentrated to dryness
  6. customThe resulting crude product is purified by flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 10:1)
  7. custom379.7 mg (54% of theory) of a colorless solid are obtained

Sources & evidence

ORD record
ord-c3dcfcffcc4548a88733ee4a6a2611f2
Source dataset
uspto-grants-2012_05
Patent number
US08173704B2

Reaction notes

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