Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → (S)-2-Ethanesulfonylamino-N-(2-{4-[2-(4-fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide

HRID 1862492Notes

Reaction equation

HRID 1862492 reaction equation
[CH2:1]([S:3]([NH:6][C@@H:7]([CH:11]([CH3:13])[CH3:12])[C:8]([OH:10])=O)(=[O:5])=[O:4])[CH3:2].Cl.[F:15][C:16]1[CH:36]=[CH:35][C:19]([O:20][CH2:21][CH2:22][O:23][C:24]2[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][NH2:32])=[CH:26][C:25]=2[O:33][CH3:34])=[CH:18][CH:17]=1.C(N(CC)C(C)C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O.O>[CH2:1]([S:3]([NH:6][C@@H:7]([CH:11]([CH3:13])[CH3:12])[C:8]([NH:32][CH2:31][CH2:30][C:27]1[CH:28]=[CH:29][C:24]([O:23][CH2:22][CH2:21][O:20][C:19]2[CH:18]=[CH:17][C:16]([F:15])=[CH:36][CH:35]=2)=[C:25]([O:33][CH3:34])[CH:26]=1)=[O:10])(=[O:4])=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 521913N,N-Diethyl-2-propanamineHCID 11356256N-ethylsulfonyl-L-valineHCID 186198462-{4-[2-(4-Fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethylamine hydrochloride

Product 1

HCID 54522274(S)-2-Ethanesulfonylamino-N-(2-{4-[2-(4-fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of (S)-2-ethanesulfonylamino-3-methyl-butyric acid (0.63 g), 2-{4-[2-(4-fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethylamine hydrochloride (1.0 g) and diethyl-isopropylamine (1.8 ml) in dimethylformamide (30 ml) is added benzotriazol-1-yloxy-tris-(dimethylamino)phosphonium hexafluorophosphate (1.5 g) in one portion. The reaction mixture is stirred for 2 hours at room temperature. Water (200 ml) is then added. The mixture is extracted with ethyl acetate (2×200 ml). The organic layers are washed with brine (2×200 ml), dried (MgSO4) and evaporated. The residue is purified by flash column chromatography on silica gel (ethyl acetate/hexane 2:1) and recrystallisation (ethyl acetate/hexane). (S)-2-Ethanesulfonylamino-N-(2-{4-[2-(4-fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide is obtained, m.p. 124-125° C.

Workup

  1. extractionThe mixture is extracted with ethyl acetate (2×200 ml)
  2. washThe organic layers are washed with brine (2×200 ml)
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. customThe residue is purified by flash column chromatography on silica gel (ethyl acetate/hexane 2:1) and recrystallisation (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-98490b228ec14c6084d253b8d3133860
Source dataset
uspto-grants-2003_03
Patent number
US06538016B2

Reaction notes

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