2-Dimethylaminopyridine → HCID 10077331, compound

HRID 732738Notes

Reaction equation

HRID 732738 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].[CH3:38][C:39]([CH3:44])([CH3:43])[C:40](Cl)=[O:41].CN(C1C=CC=CN=1)C>N1C=CC=CC=1>[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:40](=[O:41])[C:39]([CH3:44])([CH3:43])[CH3:38])[CH:15]=[CH:14]3)=[CH:9][CH:10]=1)(=[O:4])=[O:3]

Participants

5

Reactant 3

HCID 218852-DimethylaminopyridineHCID 62493Pivaloyl chlorideHCID 5327043648904-56-7

Product 1

HCID 10077331HCID 10077331, compoundYield 90.8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Dissolve the product of Example 3 (220 mg, 0.43 mmol) in pyridine (5 mL) and treat sequentially with trimethylacetyl chloride (0.144 mL, 1.17 mmol) and dimethylaminopyridine (DMAP, catalytic amount). Stir at ambient temperature for 18 hours and evaporate pyridine. Re-constitute the residue in ethyl acetate and wash with saturated aqueous NH4Cl, saturated aqueous NaHCO3, and brine. Dry the organic layer (Na2SO4), filter, and evaporate to obtain 277 mg of crude material. Pre-adsorb onto silica gel and chromatograph on a SiO2 column eluting the material with methanol in dichloromethane (0 to 6%) to give 235 mg of 2,2-dimethyl-propionic acid 6-(4-methanesulfonyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalene-2-yl ester. Dissolve the free base in a mixture of ethyl acetate and diethyl ether (20 mL; 1:1). Cool in an ice bath and treat with 2M HCl in diethyl ether (0.3 mL, 0.6 mmol). Collect the precipitate on filter paper and rinse with diethyl ether to obtain 220 mg of the title compound (80%): mass spectrum (ion spray): m/z=602.4 (M+H−HCl).

Workup

  1. customevaporate pyridine
  2. washRe-constitute the residue in ethyl acetate and wash with saturated aqueous NH4Cl, saturated aqueous NaHCO3, and brine
  3. dry with materialDry the organic layer (Na2SO4)
  4. filtrationfilter
  5. customevaporate
  6. customto obtain 277 mg of crude material
  7. washPre-adsorb onto silica gel and chromatograph on a SiO2 column eluting the material with methanol in dichloromethane (0 to 6%)

Sources & evidence

ORD record
ord-f7f07e2254d24519ae178de89e8f4fc4
Source dataset
uspto-grants-2009_09
Patent number
US07585977B2

Reaction notes

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