Water → (S)-2-(tert-butoxycarbonyl-amino)-3-methyl-butyric acid N-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-amide

HRID 1862494Notes

Reaction equation

HRID 1862494 reaction equation
[C:1]([NH:8][C@H:9]([C:13]([OH:15])=O)[CH:10]([CH3:12])[CH3:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C([N:18]([CH2:22][CH3:23])C(C)C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2N=N1.[OH2:51].CN(C)[CH:54]=[O:55]>>[C:4]([O:3][C:1](=[O:2])[NH:8][C@H:9]([C:13](=[O:15])[NH:18][CH2:22][CH2:23][C:37]1[CH:38]=[CH:39][C:34]([OH:51])=[C:35]([O:55][CH3:54])[CH:36]=1)[CH:10]([CH3:11])[CH3:12])([CH3:5])([CH3:6])[CH3:7]

Participants

6

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 83693Boc-L-ValineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 521913N,N-Diethyl-2-propanamine

Product 1

HCID 57264564(S)-2-(tert-butoxycarbonyl-amino)-3-methyl-butyric acid N-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-amide

Procedure

To a mixture of BOC-L-Valin (48 g), 4-(2-Amino-ethyl)-2-methbxy-phenol hydrochloride (45 g) and diethyl-isopropylamine (64.6 g) in dimethylformamide (900 ml) is added benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (97.8 g) in one portion. The reaction mixture is stirred for 4 hours at room temperature. Water (1000 ml) is then added. The mixture is extracted with ethyl acetate (2×500 ml). The organic layers organic layers are washed with brine (2×400 ml), dried (MgSO4) and evaporated. The residue is purified by flash column chromatography on silica gel (ethyl acetate/hexane 1:2). (S)-{1-[2-(4-Hydroxy-3-methoxy-phenyl)-ethylcarbamoyl]-2-methyl-propyl}-carbamic acid tert.-butyl ester is obtained.

Workup

  1. extractionThe mixture is extracted with ethyl acetate (2×500 ml)
  2. washThe organic layers organic layers are washed with brine (2×400 ml)
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. customThe residue is purified by flash column chromatography on silica gel (ethyl acetate/hexane 1:2)

Sources & evidence

ORD record
ord-9ab2c1b97a0b44dc8ab4180c43b952d4
Source dataset
uspto-grants-2003_03
Patent number
US06538016B2

Reaction notes

Loading…