Sodium Methoxide → 2-(1,1-dimethylethoxycarbonylamino)-N-{2-[3-methoxy-4-(4-chlorophenyl-prop-2-ynyloxy)-phenyl]-ethyl}-3-methylbutyramide

HRID 992449Notes

Reaction equation

HRID 992449 reaction equation
[CH3:1][C:2]([CH3:26])([O:4][C:5]([NH:7][CH:8]([CH:23]([CH3:25])[CH3:24])[C:9]([NH:11][CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[C:16]([O:21][CH3:22])[CH:15]=1)=[O:10])=[O:6])[CH3:3].[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]#[C:35][CH2:36]OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:30][CH:29]=1.C[O-].[Na+]>CO>[CH3:3][C:2]([CH3:26])([O:4][C:5]([NH:7][CH:8]([CH:23]([CH3:24])[CH3:25])[C:9]([NH:11][CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:36][C:35]#[C:34][C:31]2[CH:32]=[CH:33][C:28]([Cl:27])=[CH:29][CH:30]=2)=[C:16]([O:21][CH3:22])[CH:15]=1)=[O:10])=[O:6])[CH3:1]

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 184120642-(1,1-dimethylethoxycarbonylamino)-N-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-3-methylbutyramideHCID 54290153Toluene-4-sulfonic acid 3-(4-chloro-phenyl)-prop-2-ynyl ester

Product 1

HCID 186198552-(1,1-dimethylethoxycarbonylamino)-N-{2-[3-methoxy-4-(4-chlorophenyl-prop-2-ynyloxy)-phenyl]-ethyl}-3-methylbutyramide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A mixture 2-(1,1-dimethylethoxycarbonylamino)-N-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-3-methylbutyramide (4.0 g), toluene-4-sulfonic acid 3-(4-chloro-phenyl)-prop-2-ynyl ester (5.3 g) and 1M sodium methoxide solution in methanol (18 ml) in methanol (100 ml) is heated to reflux for 3 hours . Then the solvent is removed by distillation. Water (300 ml) is added. The mixture is extracted with ethyl acetate (2×200 ml) and washed with brine (100 ml). The organic layers are collected, dried (MgSO4) and evaporated. 2-(1,1-dimethylethoxycarbonylamino)-N-{2-[3-methoxy-4-(4-chlorophenyl-prop-2-ynyloxy)-phenyl]-ethyl}-3-methylbutyramide is obtained which is purified by flash column chromatography on silica gel (ethyl acetate/hexane 1:1) and recrystallisation (ethyl acetate/hexane), m.p. 141-142° C.

Workup

  1. temperatureto reflux for 3 hours
  2. customThen the solvent is removed by distillation
  3. additionWater (300 ml) is added
  4. extractionThe mixture is extracted with ethyl acetate (2×200 ml)
  5. washwashed with brine (100 ml)
  6. customThe organic layers are collected
  7. dry with materialdried (MgSO4)
  8. customevaporated

Sources & evidence

ORD record
ord-0dd7d6bb359244a3b2933ac365615d5b
Source dataset
uspto-grants-2002_10
Patent number
US06469005B1

Reaction notes

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