Ethyl bromoacetate → HCID 67359618, compound

HRID 1667175Notes

Reaction equation

HRID 1667175 reaction equation
[C:1]1([CH:7]2[CH2:12][CH2:11][CH2:10][NH:9][C:8]2=[O:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C)([O-])C.[K+].Br[CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23]>O1CCCC1.C(OCC)(=O)C.O>[O:13]=[C:8]1[CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:12][CH2:11][CH2:10][N:9]1[CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23]

Participants

6

Reactant 3

HCID 7748Ethyl bromoacetateHCID 117897263-phenylpiperidin-2-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 67359618HCID 67359618, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 22728543Water ethylacetateSolvent

Procedure

To a suspension of the product from Example 91B (1.08 g, 6.16 mmol) in tetrahydrofuran (10 mL) at 0° C. was added potassium tert-butoxide (1.0 Min tetrahydrofuran) (6.78 mL, 6.78 mmol). After stirring for 20 minutes, ethyl 2-bromoacetate (0.750 mL, 6.78 mmol) was added, and the reaction was allowed to warm to room temperature. After stirring for 3 hours, the reaction was poured in ethyl acetate/water (1:1, 200 mL). The organic layer was washed with brine (100 mL), dried over magnesium sulfate and concentrated. Silica gel chromatography using a GraceResolv 80 g silica gel column (Grace Davison Discovery Sciences) eluting with a gradient of 25% ethyl acetate/hexanes to 85% ethyl acetate/hexanes (flow=40 mL/minute) over 30 minutes supplied the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.39-7.14 (m, 5H), 4.45 (d, J=17.2, 1H), 4.23 (q, J=7.1, 2H), 3.91 (d, J=17.2, 1H), 3.78-3.65 (m, 1H), 3.65-3.49 (m, 1H), 3.41 (dt, J=5.7, 11.3, 1H), 2.32-2.12 (m, 1H), 2.12-1.74 (m, 3H), 1.30 (t, J=7.2, 3H).

Workup

  1. stirringAfter stirring for 3 hours
  2. washThe organic layer was washed with brine (100 mL)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. washeluting with a gradient of 25% ethyl acetate/hexanes to 85% ethyl acetate/hexanes (flow=40 mL/minute) over 30 minutes

Sources & evidence

ORD record
ord-69f92acc0595454b83164afa4c104d33
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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