1,2-Dichloroethane → Hydrochloric Acid

HRID 888404Notes

Reaction equation

HRID 888404 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[C:13]([C:15]([OH:18])([CH3:17])[CH3:16])[CH:12]=[C:11]([C:19](O)=[O:20])[CH:10]=1.[CH3:22][C:23]1[N:27]=[C:26]([C@H:28]([NH2:30])[CH3:29])[O:25][N:24]=1.C(Cl)C[Cl:33].C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.FC(F)(F)C(O)=O>CN(C)C=O.O>[ClH:33].[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[C:13]([C:15]([OH:18])([CH3:17])[CH3:16])[CH:12]=[C:11]([C:19]([NH:30][C@@H:28]([C:26]2[O:25][N:24]=[C:23]([CH3:22])[N:27]=2)[CH3:29])=[O:20])[CH:10]=1

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 28948822(R)-1-(3-Methyl-1,2,4-oxadiazol-5-yl)ethan-1-amineHCID 685009892',4'-Difluoro-5-(1-hydroxy-1-methylethyl)biphenyl-3-carboxylic acid

Product 2

HCID 313Hydrochloric AcidHCID 426030322',4'-Difluoro-5-(1-hydroxy-1-methylethyl)-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]biphenyl-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2′,4′-difluoro-5-(1-hydroxy-1-methylethyl)biphenyl-3-carboxylic acid (34 mg, 0.116 mmol) in N,N-dimethylformamide (1.2 mL) was added the hydrochloride salt of (1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethanamine, EDC (26.8 mg, 0.140 mmol), HOBT (17.8 mg, 0.116 mmol) and triethylamine (0.065 mL, 0.465 mmol). After 16 h, water and trifluoroacetic acid were added. The mixture was purified by reverse phase chromatography (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid). Treatment with 2 M hydrochloric acid in diethyl ether gave the title compound as a hydrochloride salt (50.1 mg). HRMS 402.1633 (M+1). 1H NMR (500 MHz, CD3OD): δ 8.03 (t, J=1.8 Hz, 1H); 7.89-7.86 (m, 2H); 7.58 (q, J=7.6 Hz, 1H); 7.12-7.07 (m, 2H); 5.46 (q, J=7.1 Hz, 1H); 2.37 (s, 3H); 1.71 (d, J=7.1 Hz, 3H); 1.61 (s, 6H).

Workup

  1. customThe mixture was purified by reverse phase chromatography (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-82364f7e033646df9a210e29190a7ef3
Source dataset
uspto-grants-2012_08
Patent number
US08247401B2

Reaction notes

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