Bromide ion → HCID 86749593, compound

HRID 1733904Notes

Reaction equation

HRID 1733904 reaction equation
[C:1]([N:9]1[CH2:18][CH2:17][C@H:16]2[C@@H:11]([CH2:12][CH2:13][C:14](=[O:19])[CH2:15]2)[CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([Mg])=[CH:23][CH:22]=1.[Br-].[Cl-].[NH4+].[OH-].[Na+]>C1COCC1>[C:1]([N:9]1[CH2:18][CH2:17][C@H:16]2[C@@H:11]([CH2:12][CH2:13][C:14]([C:24]3[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=3)([OH:19])[CH2:15]2)[CH2:10]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 259Bromide ionHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 12262834HCID 12262834, compoundHCID 178505840HCID 178505840, compound

Product 1

HCID 86749593HCID 86749593, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of trans-2-benzoyl-6-oxodecahydroisoquinoline (2.0 g, 7.8 mmol) in anhydrous THF was cooled to -78° C. with stirring under a nitrogen atmosphere. A solution of p-fluorophenylmagnesium, bromide in THF (1.0M, 7.8 mL, 7.8 mmol) was added dropwise. The reaction mixture was stirred at -78° C. for 3 h, then warmed to room temperature over 16 h. The reaction mixture was poured onto a saturated ammonium chloride solution, mixed, basified with 1N NaOH solution and extracted with ethyl acetate three times. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. Column chromatography (ethyl acetate) afforded: (1) the less polar hydroxyl epimer of the entitled product (Rf =0.52, 934 mg): mp 107°-108° C.; NMR (CDCl3, 300 MHz) 7.5-7.3(m, 7H), 7.05 (t,2H, J=7), 4.9-4.7 (m, 1H), 3.9-3.65 (m, 1H), 1.9-1.1 (m, 10H); CMR (CDCl3, 68 MHz): 170.2, 161.5 (d, J=245), 144.9, 136.1, 129.4, 128.3, 126.7, 126.1 (d, J=8), 114.7 (d, J=21), 72.9, 53.4, 48.4, 47.7, 45.0, 42.8, 41.9, 40.9, 38.0, 36.8, 32.9, 31.9, 25.3; HRMS:Calcd:353.1791, Found:353.1791; (2) a mixture of hydroxyl epimers of the entitled product (184 mg) and (3) the more polar hydroxyl epimer of the entitled product, an oil (Rf =0.41, 302 mg): NMR (CDCl3, 300 MHz): 7.55-7.3 (m, 7H), 7.05 (t, 2H, J=7), 4.9-4.6 (m, 1H), 3.9-3.6 (m, 1H), 3.1-1.0 (m, 13H); CMR (CDCl3, 68 MHz): 170.0, 166.8 (d, J=246), 135.8 (d, J=17), 129.4 (d, J=14), 128.3, 128.2, 128.1, 128.0, 126.7, 126.6, 115.0 (d, J=21), 72.4, 47.1, 44.8, 42.3, 41.6, 37.4; HRMS: Calcd 353.1791; Found:353.1791.

Workup

  1. stirringThe reaction mixture was stirred at -78° C. for 3 h
  2. additionmixed
  3. extractionextracted with ethyl acetate three times
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customColumn chromatography (ethyl acetate) afforded

Sources & evidence

ORD record
ord-d86d325cb02d41a0ac402bcbaf5a0aaf
Source dataset
uspto-grants-1996_07
Patent number
US05532243

Reaction notes

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