Imidazole → [(3S,6R)-6-(tert-butyl-dimethyl-silanyloxy)-2-oxo-azepan-3-yl]-carbamic acid tert-butyl ester

HRID 2227152Notes

Reaction equation

HRID 2227152 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:15][CH2:14][C@@H:13]([OH:16])[CH2:12][NH:11][C:10]1=[O:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Si:18](Cl)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19].N1C=CN=C1.CN(C=O)C>O>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:15][CH2:14][C@@H:13]([O:16][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[CH2:12][NH:11][C:10]1=[O:17])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 6228DimethylformamideHCID 28928tert-Butyldimethylsilyl chlorideHCID 11149222(3S,6R)-3-(tert-butoxycarbonyl)aminohexahydro-6-hydroxy-2H-azepin-2-one

Product 1

HCID 11728063[(3S,6R)-6-(tert-butyl-dimethyl-silanyloxy)-2-oxo-azepan-3-yl]-carbamic acid tert-butyl esterYield 78%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

(3S, 6R)-3-(tert-butoxycarbonyl)aminohexahydro-6-hydroxy-2H-azepin-2-one (25 g, 102 mmol), tert-butyldimethylsilyl chloride (23.16 g, 153 mmol), and imidazole (10.45 g, 153 mmol) are combined with 60 mL of DMF. The reaction is stirred at room temperature overnight. The mixture is diluted with 1 L of water. The resulting mixture is extracted with a 1:1 ( 2×200 mL) mixture of ethyl acetate and hexane. All organic layers are combined, washed with brine solution, dried with NaSO4, and concentrated. The residue is purified by recrystallization with ethyl acetate/hexane to give 28.5 g (78%) of (3S, 6R)-3-(tert-butoxycarbonyl)aminohexahydro-6-tert-butyldimethylsilyloxy-2H-azepin-2-one as a white solid; 1H NMR (CDCl3) δ5.86 (d, J=6 Hz, 1H), 5.58 (t, J=6 Hz, 1H), 4.18 (m, 1H), 3.91 (s, 1H), 3.35(dd, J=6 Hz and 16 Hz, 1H), 3.07 (m, 1H), 1.80 (m, 4H), 1.40 (s, 9H), 0.83 (s, 9H), 0.004 (s, 6H).

Workup

  1. extractionThe resulting mixture is extracted with a 1:1 ( 2×200 mL) mixture of ethyl acetate and hexane
  2. washwashed with brine solution
  3. dry with materialdried with NaSO4
  4. concentrationconcentrated
  5. customThe residue is purified by recrystallization with ethyl acetate/hexane

Sources & evidence

ORD record
ord-c4d79dcd812f4d35bdc75fcd19bcd3e7
Source dataset
uspto-grants-2002_07
Patent number
US06413954B1

Reaction notes

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