Imidazole → (S)-8-Benzyloxy-4-[dimethyl-(1,1,2-trimethyl-propyl)-silanyloxymethyl]-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one

HRID 506661Notes

Reaction equation

HRID 506661 reaction equation
C(O[C:4]([C:6]1[N:7]([C@@H:23]([CH2:35][NH:36]C(OC(C)(C)C)=O)[CH2:24][O:25][Si:26]([CH3:34])([CH3:33])C(C)(C)C(C)C)[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[CH:10][CH:9]=2)=[O:5])C.N1[CH:48]=[CH:47]N=C1.C[Si](Cl)(C)[CH2:51][CH2:52][CH2:53]CCC.[CH3:59]N(C)C=O>>[CH2:16]([O:15][C:11]1[CH:12]=[CH:13][C:8]2[N:7]3[C@H:23]([CH:24]([C:47]([CH3:48])([CH3:59])[CH:52]([CH3:53])[CH3:51])[O:25][SiH:26]([CH3:33])[CH3:34])[CH2:35][NH:36][C:4](=[O:5])[C:6]3=[CH:14][C:9]=2[CH:10]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 4

HCID 795ImidazoleHCID 6228DimethylformamideHCID 2733540Chloro(hexyl)dimethylsilaneHCID 684609625-benzyloxy-1-{(S)-1-(tert-butoxycarbonylamino-methyl)-2-[dimethyl-(1,1,2-trimethyl-propyl)-silanyloxy]-ethyl}-1H-indole-2-carboxylic acid ethyl ester

Product 1

HCID 131727591(S)-8-Benzyloxy-4-[dimethyl-(1,1,2-trimethyl-propyl)-silanyloxymethyl]-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-oneYield 35%

Procedure

The title compound was synthesized in analogy to example 8, intermediate a), from 5-benzyloxy-1-{(S)-1-(tert-butoxycarbonylamino-methyl)-2-[dimethyl-(1,1,2-trimethyl-propyl)-silanyloxy]-ethyl}-1H-indole-2-carboxylic acid ethyl ester to give a mixture of the desired compound and the unprotected hydroxymethyl compound. The mixture was dissolved in N,N-dimethylformamide and 1 equivalent of imidazole was added. At 0° C., 1 equivalent of dimethylhexylsilyl chloride was added and the cooling bath was removed. The reaction mixture was poured on water and was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography over silica gel using n-hexane:ethyl acetate (1:2 v/v) as eluant to give the desired product as a light yellow foam (35%).

Workup

  1. customto give
  2. additiona mixture of the desired compound
  3. customthe cooling bath was removed
  4. additionThe reaction mixture was poured on water
  5. extractionwas extracted twice with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by column chromatography over silica gel

Sources & evidence

ORD record
ord-b84d78024085419ba4dd82cb99e1ad27
Source dataset
uspto-grants-2010_08
Patent number
US07786109B2

Reaction notes

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