Ammonium Chloride → Methyl 4-{(4E)-5-(5-fluoro-2-hydroxyphenyl)-3-[4-(methoxycarbonyl)benzyl]pent-4-en-1-yl}benzoate

HRID 1512207Notes

Reaction equation

HRID 1512207 reaction equation
C([Li])CCC.[Br-].[F:7][C:8]1[CH:9]=[CH:10][C:11]([OH:34])=[C:12]([CH:33]=1)[CH2:13][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[CH:35]([CH:37]([CH2:49][CH2:50][C:51]1[CH:60]=[CH:59][C:54]([C:55]([O:57][CH3:58])=[O:56])=[CH:53][CH:52]=1)[CH2:38][C:39]1[CH:48]=[CH:47][C:42]([C:43]([O:45][CH3:46])=[O:44])=[CH:41][CH:40]=1)=O.[Cl-].[NH4+]>CCCCCC.C1COCC1.O.C(OCC)(=O)C>[F:7][C:8]1[CH:9]=[CH:10][C:11]([OH:34])=[C:12](/[CH:13]=[CH:35]/[CH:37]([CH2:38][C:39]2[CH:40]=[CH:41][C:42]([C:43]([O:45][CH3:46])=[O:44])=[CH:47][CH:48]=2)[CH2:49][CH2:50][C:51]2[CH:60]=[CH:59][C:54]([C:55]([O:57][CH3:58])=[O:56])=[CH:53][CH:52]=2)[CH:33]=1

Participants

9

Reactant 4

HCID 25517Ammonium ChlorideHCID 59180526Dimethyl 4,4'-(2-formylbutane-1,4-diyl)dibenzoateHCID 86638793(5-Fluoro-2-hydroxybenzyl)(triphenyl)phosphonium bromideHCID 178418339Butyllithium

Product 1

HCID 59180513Methyl 4-{(4E)-5-(5-fluoro-2-hydroxyphenyl)-3-[4-(methoxycarbonyl)benzyl]pent-4-en-1-yl}benzoate

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

At 0° C., 21.65 ml (54.12 mmol) of a 2.5 M solution of n-butyllithium in hexane are slowly added dropwise to a solution of 10.84 g (23.2 mmol) of (5-fluoro-2-hydroxybenzyl)(triphenyl)-phosphonium bromide in 150 ml of THF, and the mixture is stirred at this temperature for 45 min. At this temperature, 6.85 g (19.33 mmol) of dimethyl 4,4′-(2-formylbutane-1,4-diyl)dibenzoate in 100 ml of THF are then metered in slowly. The reaction solution is stirred at 0° C. for 3 h, saturated ammonium chloride solution is then added, the mixture is diluted with water and ethyl acetate, the organic phase is separated off and the aqueous phase is re-extracted twice with ethyl acetate. The combined organic phases are dried over sodium sulfate and filtered, and the solvent is removed to dryness. The crude product obtained is purified by flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 4:1). This gives 8.21 g (17.75 mmol, 76% of theory) of a yellowish oil.

Workup

  1. stirringThe reaction solution is stirred at 0° C. for 3 h
  2. customthe organic phase is separated off
  3. extractionthe aqueous phase is re-extracted twice with ethyl acetate
  4. dry with materialThe combined organic phases are dried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent is removed to dryness

Sources & evidence

ORD record
ord-880e9d5de1fb4c27965ad2919d7ebd3c
Source dataset
uspto-grants-2012_07
Patent number
US08217063B2

Reaction notes

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