Thioglycolic Acid → methyl 3-[4-({4-[(3,5-diphenyl-1H-pyrazol-1-yl)methyl]benzyl}amino)phenyl]propanoate

HRID 508037Notes

Reaction equation

HRID 508037 reaction equation
[N+](C1C=CC=CC=1S([NH:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[CH:16][CH:15]=1)(=O)=O)([O-])=O.[C:26]1([C:32]2[CH:36]=[C:35]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[N:34]([CH2:43][C:44]3[CH:49]=[CH:48][C:47]([CH2:50]O)=[CH:46][CH:45]=3)[N:33]=2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.SCC(O)=O.O.[OH-].[Li+].C(=O)([O-])O.[Na+]>ClCCl.CN(C)C=O>[C:26]1([C:32]2[CH:36]=[C:35]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[N:34]([CH2:43][C:44]3[CH:49]=[CH:48][C:47]([CH2:50][NH:13][C:14]4[CH:15]=[CH:16][C:17]([CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[CH:18][CH:19]=4)=[CH:46][CH:45]=3)[N:33]=2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

10

Reactant 7

HCID 1133Thioglycolic AcidHCID 11776TriphenylphosphineHCID 168937Lithium hydroxide, monohydrateHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 516892Sodium BicarbonateHCID 23157467Methyl 3-(4-{[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoateHCID 23157492{4-[(3,5-diphenyl-1H-pyrazol-1-yl)methyl]phenyl}methanol

Product 1

HCID 23157561methyl 3-[4-({4-[(3,5-diphenyl-1H-pyrazol-1-yl)methyl]benzyl}amino)phenyl]propanoateYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl 3-(4-{[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoate (180 mg, 0.5 mmol), {4-[(3,5-diphenyl-1H-pyrazol-1-yl)methyl]phenyl}methanol (178 mg, 0.5 mmol) and triphenylphosphine (262 mg, 1.0 mmol) in dichloromethane (5 mL) was added diethyl azodicarboxylate (40% toluene solution, 435 mg, 1.0 mmol) at room temperature, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was purified by silica gel column chromatography (10%-80% ethyl acetate/hexane) to give a yellow oil. To a solution of the yellow oil and mercaptoacetic acid (100 mg, 1.1 mmol) in N,N-dimethylformamide (5 mL) was added lithium hydroxide monohydrate (80 mg, 1.9 mmol), and the mixture was stirred at room temperature for 14 hr. The reaction mixture was poured into 10% aqueous sodium hydrogencarbonate solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried using a Presep Dehydration tube (manufactured by Wako Pure Chemical Industries, Ltd.), and concentrated. The residue was purified by silica gel column chromatography (10%-80% ethyl acetate/hexane) to give the title compound (120 mg, yield 48%, 2 steps) as a yellow oil.

Workup

  1. customThe reaction mixture was purified by silica gel column chromatography (10%-80% ethyl acetate/hexane)
  2. customto give a yellow oil
  3. stirringthe mixture was stirred at room temperature for 14 hr
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialThe ethyl acetate layer was dried
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography (10%-80% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9fd5172ec0574a25b6292cd7592826df
Source dataset
uspto-grants-2010_08
Patent number
US07786165B2

Reaction notes

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