Benzoyl chloride → HCID 10394116, compound

HRID 732739Notes

Reaction equation

HRID 732739 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([O:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][N:32]4[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]4)=[CH:25][CH:24]=3)=[C:13]3[C:18](=[CH:19][CH:20]=2)[CH:17]=[C:16]([OH:21])[CH:15]=[CH:14]3)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[C:38](Cl)(=[O:45])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>N1C=CC=CC=1.CN(C1C=CN=CC=1)C>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[C:12]([O:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][N:32]4[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]4)=[CH:25][CH:24]=3)=[C:13]3[C:18](=[CH:19][CH:20]=2)[CH:17]=[C:16]([O:21][C:38](=[O:45])[C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:15]=[CH:14]3)=[CH:9][CH:10]=1)(=[O:4])=[O:3]

Participants

5

Reactant 2

HCID 7412Benzoyl chlorideHCID 5327043648904-56-7

Product 1

HCID 10394116HCID 10394116, compoundYield 97.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

Dissolve the product of Example 3 (220 mg, 0.43 mmol) in pyridine (5 mL) and treat sequentially with benzoyl chloride (0.067 mL, 0.58 mmol), and DMAP (catalytic amount). Stir at ambient temperature for 18 hours and evaporate pyridine. Partition between saturated aqueous NH4Cl and ethyl acetate (containing 8% MeOH). After separation of the layers extract the aqueous layer with ethyl acetate (containing 5% MeOH) and combine the two organic layers. Wash with saturated aqueous NaHCO3 and brine. Dry the organic layer (Na2SO4), filter, and evaporate to obtain 276 mg of crude free base material. Pre-adsorb on to silica gel and chromatograph on a SiO2 column eluting with methanol in dichloromethane (0 to 6%) to give 260 mg of benzoic acid 6-(4-methanesulfonyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-yl ester. Dissolve the free base in hot ethyl acetate (20 mL) and dilute with diethyl ether (20 mL). Cool in an ice bath and treat with 2M HCl in diethyl ether (0.31 mL, 0.62 mmol). Collect the precipitate on filter paper and rinse with diethyl ether to obtain 255 mg of the title compound (91%): mass spectrum (ion spray): m/z=622.3 (M+H−HCl).

Workup

  1. customevaporate pyridine
  2. customPartition between saturated aqueous NH4Cl and ethyl acetate (containing 8% MeOH)
  3. customAfter separation of the layers
  4. extractionextract the aqueous layer with ethyl acetate (containing 5% MeOH)
  5. washWash with saturated aqueous NaHCO3 and brine
  6. dry with materialDry the organic layer (Na2SO4)
  7. filtrationfilter
  8. customevaporate
  9. customto obtain 276 mg of crude free base material
  10. washPre-adsorb on to silica gel and chromatograph on a SiO2 column eluting with methanol in dichloromethane (0 to 6%)

Sources & evidence

ORD record
ord-aa3fb125c0104f11bc8c8301fbf7491d
Source dataset
uspto-grants-2009_09
Patent number
US07585977B2

Reaction notes

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