Water → [(3S,6R)-6-(tert-butyl-dimethyl-silanyloxy)-2-oxo-1-pyridin-3-ylmethyl-azepan-3-yl]-carbamic acid tert-butyl ester

HRID 2224019Notes

Reaction equation

HRID 2224019 reaction equation
[C:1]([O:5][C:6](=[O:24])[NH:7][C@H:8]1[CH2:14][CH2:13][C@@H:12]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH2:11][NH:10][C:9]1=[O:23])([CH3:4])([CH3:3])[CH3:2].Cl.Cl[CH2:27][C:28]1[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=1.O>C1COCC1>[C:1]([O:5][C:6](=[O:24])[NH:7][C@H:8]1[CH2:14][CH2:13][C@@H:12]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH2:11][N:10]([CH2:27][C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)[C:9]1=[O:23])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 962WaterHCID 233943-(Chloromethyl)pyridine hydrochlorideHCID 11728063[(3S,6R)-6-(tert-butyl-dimethyl-silanyloxy)-2-oxo-azepan-3-yl]-carbamic acid tert-butyl ester

Product 1

HCID 69268061[(3S,6R)-6-(tert-butyl-dimethyl-silanyloxy)-2-oxo-1-pyridin-3-ylmethyl-azepan-3-yl]-carbamic acid tert-butyl esterYield 100.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of [(3S,6R)-6-(tert-butyl-dimethyl-silanyloxy)-2-oxo-azepan-3-yl]-carbamic acid tert-butyl ester (4.0 g, 11.1 mmol) in THF (30 mL) at −78° C. is added KN(Si(CH3)3)2 (45.0 mL 1M THF, 45.0 mmol) slowly. The mixture is stirred at room temperature for 20 min, cooled to −78° C., and 3-chloromethyl-pyridine hydrochloride (2.75 g, 16.7 mmol) is added in portions. The reaction is warmed to room temperature and stirred for 16 h, H2O (20 mL) is added and the mixture is partitioned with H2O/ether, the organic layer is separated, dried with Na2SO4 and evaporated to give a white solid, 5.0 g (quantitative) of [(3S,6R)-6-(tert-butyl-dimethyl-silanyloxy)-2-oxo-1-pyridin-3-ylmethyl-azepan-3-yl]-carbamic acid tert-butyl ester. MS (ESI) 899.3 (2M+H)+

Workup

  1. temperaturecooled to −78° C.
  2. temperatureThe reaction is warmed to room temperature
  3. stirringstirred for 16 h
  4. customthe mixture is partitioned with H2O/ether
  5. customthe organic layer is separated
  6. dry with materialdried with Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-d3d6753766854c0fa0aa228f1dcc9db3
Source dataset
uspto-grants-2008_05
Patent number
US07378410B2

Reaction notes

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