Imidazole → HCID 90326879, compound

HRID 716181Notes

Reaction equation

HRID 716181 reaction equation
O[C@H]1[C@H](O)CCN(C(OCC2C=CC=CC=2)=O)C1.[Si:19]([O:26][C@@H:27]1[C@@H:32]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[CH2:31][CH2:30][N:29]([C:41]([O:43][CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[O:42])[CH2:28]1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].C([Si](C)(C)Cl)(C)(C)C.N1C=CN=C1>CN(C=O)C.O>[Si:19]([O:26][C@H:27]1[C@H:32]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[CH2:31][CH2:30][N:29]([C:41]([O:43][CH2:44][C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)=[O:42])[CH2:28]1)([C:22]([CH3:23])([CH3:24])[CH3:25])([CH3:21])[CH3:20].[Si:19]([O:26][C@@H:27]1[C@@H:32]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[CH2:31][CH2:30][N:29]([C:41]([O:43][CH2:44][C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)=[O:42])[CH2:28]1)([C:22]([CH3:23])([CH3:24])[CH3:25])([CH3:21])[CH3:20]

Participants

8

Reactant 4

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 57370416HCID 57370416, compoundHCID 90326879HCID 90326879, compound

Product 2

HCID 90326879HCID 90326879, compoundYield 111.6%HCID 90326881HCID 90326881, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

benzyl (3R,4R)-3,4-bis((tert-butyl(dimethyl)silyl)oxy)-1-piperidinecarboxylate and benzyl (3S,4S)-3,4-bis((tert-butyl(dimethyl)silyl)oxy)-1-piperidinecarboxylate (1/1). Benzyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (5.00 g, 21.44 mmol, Bioorg. Med. Chem. Lett. 2007, 17, 1254) in 5% K2CO3 in 1/1 EtOH/H2O (214 mL) was heated at reflux for 3 h. After cooling to RT, the mixture was concentrated. EtOH (300 mL) was added to the liquid and removed in vacuo. The resulting solid was extracted with CHCl3 (2×250 mL). The combined CHCl3 fractions were dried over anh. Na2SO4, filtered and concentrated to give benzyl (3R,4R)-3,4-dihydroxy-1-piperidinecarboxylate and benzyl (3S,4S)-3,4-dihydroxy-1-piperidinecarboxylate (1/1) (5.98 g) as a light yellow syrup. MS (ESI, pos. ion) m/z: 252.1 [M+H]. A heterogenous mixture of benzyl (3R,4R)-3,4-dihydroxy-1-piperidinecarboxylate and benzyl (3S,4S)-3,4-dihydroxy-1-piperidinecarboxylate (1/1) (5.98 g, 23.80 mmol), tert-butyldimethylchlorosilane (10.76 g, 71.4 mmol) and imidazole (7.85 mL, 119 mmol) in DMF (24 mL) was stirred at RT overnight. H2O (300 mL) was added and the mixture was extracted with Et2O (3×100 mL). The combined organic layers were washed with H2O (300 mL) followed by brine (200 mL) and dried over anh. Na2SO4, filtered and concentrated. The crude material was purified by silica gel chromatography (0-20% EtOAc in hexanes) to provide benzyl (3R,4R)-3,4-bis((tert-butyl(dimethyl)silyl)oxy)-1-piperidinecarboxylate and benzyl (3S,4S)-3,4-bis((tert-butyl(dimethyl)silyl)oxy)-1-piperidinecarboxylate (1/1) (6.37 g, 13.28 mmol, 62% yield over two steps) as a clear, colorless oil. MS (ESI, pos. ion) m/z: 480.1 [M+H].

Workup

  1. extractionthe mixture was extracted with Et2O (3×100 mL)
  2. washThe combined organic layers were washed with H2O (300 mL)
  3. dry with materialdried over anh. Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by silica gel chromatography (0-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-f7eecc93fe154fe28f9f6b32707a0d3d
Source dataset
uspto-grants-2015_11
Patent number
US09187486B2

Reaction notes

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