Triphenylphosphine → ethyl 3-(4-{{4-[(3,5-diphenyl-1H-pyrazol-1-yl)methyl]-3-isopropoxybenzyl}[(2-nitrophenyl)sulfonyl]amino}-2,6-difluorophenyl)propanoate

HRID 508101Notes

Reaction equation

HRID 508101 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N+:18]([O-:20])=[O:19])(=[O:11])=[O:10])[CH:5]=[C:4]([F:21])[C:3]=1[CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25].[C:29]1([C:35]2[CH:39]=[C:38]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[N:37]([CH2:46][C:47]3[CH:52]=[CH:51][C:50]([CH2:53]O)=[CH:49][C:48]=3[O:55][CH:56]([CH3:58])[CH3:57])[N:36]=2)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[C:29]1([C:35]2[CH:39]=[C:38]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[N:37]([CH2:46][C:47]3[CH:52]=[CH:51][C:50]([CH2:53][N:8]([S:9]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=4[N+:18]([O-:20])=[O:19])(=[O:10])=[O:11])[C:6]4[CH:5]=[C:4]([F:21])[C:3]([CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=[C:2]([F:1])[CH:7]=4)=[CH:49][C:48]=3[O:55][CH:56]([CH3:58])[CH3:57])[N:36]=2)[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 23157278HCID 23157278, compoundHCID 23157461HCID 23157461, compound

Product 1

HCID 23157336ethyl 3-(4-{{4-[(3,5-diphenyl-1H-pyrazol-1-yl)methyl]-3-isopropoxybenzyl}[(2-nitrophenyl)sulfonyl]amino}-2,6-difluorophenyl)propanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of ethyl 3-(2,6-difluoro-4-{[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoate (0.425 g, 1.03 mmol), {4-[(3,5-diphenyl-1H-pyrazol-1-yl)methyl]-3-isopropoxyphenyl}methanol (0.315 g, 0.790 mmol) and triphenylphosphine (0.312 g, 1.19 mmol) in tetrahydrofuran (15 mL) was stirred at room temperature, diethyl azodicarboxylate (40% toluene solution, 0.540 mL, 1.19 mmol) was added and the mixture was stirred for 16 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (20%-80% ethyl acetate/hexane) to give ethyl 3-(4-{{4-[(3,5-diphenyl-1H-pyrazol-1-yl)methyl]-3-isopropoxybenzyl}[(2-nitrophenyl)sulfonyl]amino}-2,6-difluorophenyl)propanoate as a yellow oil. To a solution of the obtained oil and mercaptoacetic acid (0.169 g, 1.84 mmol) in N,N-dimethylformamide (15 mL) was added lithium hydroxide monohydrate (0.154 g, 3.68 mmol), and the mixture was stirred at room temperature for 2 hr. Ethyl acetate was added to the residue, and the mixture was washed with saturated aqueous sodium hydrogencarbonate and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (5%-40% ethyl acetate/hexane) to give the title compound (0.431 g, yield 90%, 2 steps) as a yellow oil.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue was purified by silica gel column chromatography (20%-80% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9a77dd8f1d454fa29bfaae402030a260
Source dataset
uspto-grants-2010_08
Patent number
US07786165B2

Reaction notes

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