Triethylamine → HCID 14988197, compound

HRID 1648338Notes

Reaction equation

HRID 1648338 reaction equation
Br[CH:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][C:7]([O:13][Si:14]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:17])[CH3:16])=[CH:8][CH:9]=2)[O:4][CH2:3]1.BrC1(Br)C(=O)C2C(=CC(O[Si](C(C)C)(C(C)C)C(C)C)=CC=2)OC1.[OH:48][C:49]1([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1.C(N(CC)CC)C>C(O)C>[OH:48][C:49]1([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[CH2:54][CH2:53][N:52]([CH:2]2[C:11](=[O:12])[C:10]3[C:5](=[CH:6][C:7]([O:13][Si:14]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:17])[CH3:16])=[CH:8][CH:9]=3)[O:4][CH2:3]2)[CH2:51][CH2:50]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 963874-Phenylpiperidin-4-olHCID 10600708HCID 10600708, compoundHCID 19919715HCID 19919715, compound

Product 1

HCID 14988197HCID 14988197, compoundYield 3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

7-(Triisopropylsilyloxy)-4-chromanone (2.0 g, 6.2 mmol) was dissolved in CCl4 (45 ml). Bromine (0.3 ml, 6.4 mmol) in CCl4 (5 ml) was added dropwise at ambient temperature over 10 minutes. The reaction initially turned dark red but after stirring for 10 minutes the color changed to light yellow. This yellow solution was washed with dilute NaHSO3, saturated NaHCO3 and brine, dried by filtering through phase separatory paper, and concentrated to yield a brown oil (2.3 g, 93%) which NMR showed was a 2.5:1:1 mixture of 3-bromo-7-(triisopropylsilyloxy)-4-chromanone, 3,3-dibromo-7-(triisopropylsilyloxy)-4-chromanone and starting material. This crude mixture (2.3 g, 5.6 mmol) was combined with 4-hydroxy-4-phenyl piperidine (1.0 g, 5.8 mmol), triethylamine (0.9 ml, 6.5 mmol) and ethanol (50 ml). The reaction was refluxed for 3 hours, then cooled and concentrated. The residue was partitioned between ethyl acetate and water. The organic layer was washed with water and brine, dried over CaSO4, concentrated and the residue chromatographed on silica gel using gradient elution with ethyl acetate/hexanes to give 80 mg (3%) of present title product as a yellow solid, mp 132°-132.5° C.

Workup

  1. temperatureThe reaction was refluxed for 3 hours
  2. temperaturecooled
  3. concentrationconcentrated
  4. customThe residue was partitioned between ethyl acetate and water
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over CaSO4
  7. concentrationconcentrated
  8. customthe residue chromatographed on silica gel using gradient elution with ethyl acetate/hexanes

Sources & evidence

ORD record
ord-c581556a88154c8cb27cddc078a9c29d
Source dataset
uspto-grants-1995_07
Patent number
US05436255

Reaction notes

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