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

HRID 2105346Notes

Reaction equation

HRID 2105346 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.N1C=CN=C1.C[Si](Cl)(C)[C:51]([CH:54]([CH3:56])[CH3:55])([CH3:53])[CH3:52]>CN(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:51]([CH3:53])([CH3:52])[CH:54]([CH3:56])[CH3:55])[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 3

HCID 795ImidazoleHCID 144239Dimethylthexylsilyl chlorideHCID 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%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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 dimethylthexylsilyl 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-1f504293a09440c6829d5d38ef63867a
Source dataset
uspto-grants-2009_08
Patent number
US07579351B2

Reaction notes

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