Water → HCID 57504911, compound

HRID 2060782Notes

Reaction equation

HRID 2060782 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8](=O)[CH2:9][CH:10]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH2:11][CH:12]=[CH2:13])[CH:5]=[CH:6][CH:7]=1.[CH2:23]([NH:30][OH:31])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.O.C(OCC)(=O)C>C1COCC1>[CH2:23]([N:30]1[C:8]2([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=3)[CH2:9][CH:10]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH2:11][CH:12]2[CH2:13][O:31]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 2794173BenzylhydroxylamineHCID 57475822HCID 57475822, compound

Product 1

HCID 57504911HCID 57504911, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 1-(3-bromophenyl)-3-(tert-butyldimethylsilyloxy)hex-5-en-1-one (6.84 g, 17.8 mmol) and N-benzylhydroxylamine (2.86 g, 23.2 mmol) in THF (60 mL) is added Ti(OEt)4 (8.14 g, 35.7 mmol). The reaction mixture is heated to 70° C. in a sealed tube. After 2 h, the temperature is increased to 80° C. and stirring is continued for 3 days. The reaction mixture is cooled to room temperature. Water and ethyl acetate are added and the mixture is stirred vigorously for 15 minutes. The solids are allowed to settle and the organic and aqueous layers are decanted through a pad of diatomaceous earth. The layers are separated and the aqueous layer is extracted three times with ethyl acetate. The combined organic layers are washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product is purified by silica gel chromatography eluting with 0% to 20% ethyl acetate in hexanes gradient over 20 minutes to give the title compound as a diastereomeric mixture (7.42 g, 85%). ES/MS m/e (79Br/81Br) 488, 490 (M+1).

Workup

  1. temperaturethe temperature is increased to 80° C.
  2. waitis continued for 3 days
  3. temperatureThe reaction mixture is cooled to room temperature
  4. stirringthe mixture is stirred vigorously for 15 minutes
  5. customthe organic and aqueous layers are decanted through a pad of diatomaceous earth
  6. customThe layers are separated
  7. extractionthe aqueous layer is extracted three times with ethyl acetate
  8. washThe combined organic layers are washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe crude product is purified by silica gel chromatography
  13. washeluting with 0% to 20% ethyl acetate in hexanes
  14. waitgradient over 20 minutes

Sources & evidence

ORD record
ord-7bb0ae9e06104c06b0cde3eba08b9ba9
Source dataset
uspto-grants-2012_10
Patent number
US08278441B2

Reaction notes

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