Ethyl bromoacetate → (3S-cis)-Hexahydro-3-[[(1,1-dimethylethoxy)-carbonyl]amino]-7-methyl-2-oxo-1H-azepine-1-acetic acid, ethyl ester

HRID 1199

Reaction equation

HRID 1199 reaction equation
[CH3:1][C:2]([CH3:17])([O:4][C:5]([NH:7][C@H:8]1[CH2:14][CH2:13][CH2:12][C@@H:11]([CH3:15])[NH:10][C:9]1=[O:16])=[O:6])[CH3:3].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31]>O1CCCC1>[CH3:3][C:2]([CH3:1])([O:4][C:5]([NH:7][C@H:8]1[CH2:14][CH2:13][CH2:12][C@@H:11]([CH3:15])[N:10]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])[C:9]1=[O:16])=[O:6])[CH3:17]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 2733832Lithium HexamethyldisilazideHCID 14927375(3S-cis)-hexahydro-3-[[(1,1-dimethylethoxy)carbonyl]amino]-7-methyl-2H-azepin-2-one

Product 1

HCID 14927378(3S-cis)-Hexahydro-3-[[(1,1-dimethylethoxy)-carbonyl]amino]-7-methyl-2-oxo-1H-azepine-1-acetic acid, ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (3S-cis)-hexahydro-3-[[(1,1-dimethylethoxy)carbonyl]amino]-7-methyl-2H-azepin-2-one [prepared as described in Example 64(f), 500 mg., 2.06 mmol.] in tetrahydrofuran (13 ml.) at room temperature under argon was treated dropwise with 1.0M lithium bis(trimethylsilyl)amide in tetrahydrofuran (2.7 ml., 2.7 mmol.) immediately followed by the dropwise addition of ethyl bromoacetate (0.47 ml., 4.21 mmol.). The resulting mixture was stirred for 30 minutes, quenched with aqueous ammonium chloride, diluted with water and extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried (sodium sulfate), filtered and concentrated to a yellow oil. Following flash chromatography (E Merck silica gel) eluting with 2:1 hexane/ethyl acetate, 750 mg. of title product was obtained as a light yellow oil; TLC (1:1 ethyl acetate:hexane) Rf =0.52.

Workup

  1. customquenched with aqueous ammonium chloride
  2. additiondiluted with water
  3. extractionextracted twice with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated to a yellow oil
  8. washeluting with 2:1 hexane/ethyl acetate, 750 mg

Sources & evidence

ORD record
ord-276860cf665e4f20bd9d6fbcfc7e8c12
Source dataset
uspto-grants-1998_03
Patent number
US05723457

Linked notes

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