(+/-)-(2R,3R)-1-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-[(1R)-1-(3-chloro-4-cyano-2-methylphenylamino)ethyl]piperidine → 4-[(1S,7R,7aR)-7-Hydroxy-1-methyl-3-oxohexahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile

HRID 751173Notes

Reaction equation

HRID 751173 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12]C[C@@H:10]([O:14][Si](C(C)(C)C)(C)C)[C@H:9]1[C@H:22]([NH:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[C:27]([Cl:33])[C:26]=1[CH3:34])[CH3:23])=[O:7])(C)(C)C.C(OC(N1CCC[C@@H](O[Si](C(C)(C)C)(C)C)[C@H]1[C@@H](NC1C=CC(C#N)=C(Cl)C=1C)C)=O)(C)(C)C>>[OH:14][C@H:10]1[C@@H:9]2[N:8]([C:6](=[O:7])[N:24]([C:25]3[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[C:27]([Cl:33])[C:26]=3[CH3:34])[C@H:22]2[CH3:23])[CH2:13][CH2:12]1

Participants

3

Reactant 2

HCID 59754211(+/-)-(2R,3R)-1-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-[(1R)-1-(3-chloro-4-cyano-2-methylphenylamino)ethyl]piperidineHCID 59754325(+/-) (2R,3R)-1-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-[(1S)-1-(3-chloro-4-cyano-2-methylphenylamino)ethyl]piperidine

Product 1

HCID 167315144-[(1S,7R,7aR)-7-Hydroxy-1-methyl-3-oxohexahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile

Procedure

Compounds 81A-a and 81A-b were synthesized from 1-tert-butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-formyl-piperidine (18F) following a procedure similar to that used for 80F to give a mixture of 81A-a and 81A-b as the crude product. Purification and separation by flash chromatography (12 g ISCO silica gel column, 0-20% EtOAc/hexane gradient) provided 81A-a as colorless film (28 mg) and 81A-b (14 mg) as a colorless film. For 81A-a: HPLC (Phenomenex Luna 5 u C18 4.6×50 mm, linear gradient over 4 min) retention time 4.85 min (100%); MS (ES) m/z 508.0 [M+H]+; HRMS calcd for C26H43ClN3O3Si 508.2762, Found 508.2761. For 81A-b: HPLC (Phenomenex Luna 5 u C18 4.6×50 mm, linear gradient over 4 min) retention time 4.95 min (100%); MS (ES) m/z 508.0 [M+H]+; HRMS calcd for C26H43ClN3O3Si 508.2762, Found 508.2748.

Workup

  1. customHPLC (Phenomenex Luna 5 u C18 4.6×50 mm, linear gradient over 4 min) retention time 4.85 min (100%)
  2. customHPLC (Phenomenex Luna 5 u C18 4.6×50 mm, linear gradient over 4 min) retention time 4.95 min (100%)

Sources & evidence

ORD record
ord-38e6701c908144eda49c7079b4d227c0
Source dataset
uspto-grants-2008_07
Patent number
US07405234B2

Reaction notes

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