Ethyl Acetate → Ethyl (1-benzyl-4-hydroxyazepan-4-yl)acetate

HRID 383939Notes

Reaction equation

HRID 383939 reaction equation
C([Li])CCC.[CH2:6]([N:13]1[CH2:19][CH2:18][CH2:17][C:16](=[O:20])[CH2:15][CH2:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[NH4+].[Cl-].[CH3:23][CH2:24][O:25][C:26]([CH3:28])=[O:27]>C1COCC1.CCCCCC.O>[CH2:6]([N:13]1[CH2:19][CH2:18][CH2:17][C:16]([CH2:28][C:26]([O:25][CH2:24][CH3:23])=[O:27])([OH:20])[CH2:15][CH2:14]1)[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

8

Reactant 4

HCID 8857Ethyl Acetate2×HCID 25517Ammonium ChlorideHCID 15143501-Benzyl-hexahydro-4H-azepin-4-oneHCID 178418339Butyllithium

Product 1

HCID 59291435Ethyl (1-benzyl-4-hydroxyazepan-4-yl)acetate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of DIPA (3.1 mL) in THF (30 mL) was added dropwise a 2.6 M solution (8.6 mL) of n-butyl lithium in hexane at −70° C. After stirring at 0° C. for 40 minutes, EtOAc (2.3 mL) was added dropwise thereto at −70° C., followed by stirring for 5 minutes. A solution of 1-benzylazepan-4-one (3.6 g) in THF (10 mL) was added dropwise thereto, followed by stirring for 40 minutes. To the reaction mixture was added a saturated aqueous NH4Cl solution, followed by addition of water and extraction with EtOAc. The organic layer was washed with brine, dried over MgSO4, and then concentrated under reduced pressure. The residue was purified by medium-pressure preparative liquid chromatography (silica gel, YAMAZEN YFLC WPrep2XY, CHCl3:MeOH: aqueous ammonia) to obtain ethyl (1-benzyl-4-hydroxyazepan-4-yl)acetate (5.0 g) as a yellow oily substance.

Workup

  1. customat −70° C.
  2. stirringby stirring for 5 minutes
  3. stirringby stirring for 40 minutes
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by medium-pressure preparative liquid chromatography (silica gel, YAMAZEN YFLC WPrep2XY, CHCl3:MeOH: aqueous ammonia)

Sources & evidence

ORD record
ord-66eee50a1cec47b39b7b99f201a7169b
Source dataset
uspto-grants-2013_02
Patent number
US08367696B2

Reaction notes

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