Lithium Bromide → 1-(2-Chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)-4-(1,1-dimethylethyl)piperidin-4-ol

HRID 1490208Notes

Reaction equation

HRID 1490208 reaction equation
[Br-].[Li+].[C:3]([Li])([CH3:6])([CH3:5])[CH3:4].[Cl:8][C:9]1[CH:22]=[CH:21][C:20]2[CH:19]3[CH2:23][C:12]([CH2:24][N:25]4[CH2:30][CH2:29][C:28](=[O:31])[CH2:27][CH2:26]4)([C:13]4[C:18]3=[CH:17][CH:16]=[CH:15][CH:14]=4)[C:11]=2[CH:10]=1>O1CCCC1>[Cl:8][C:9]1[CH:22]=[CH:21][C:20]2[CH:19]3[CH2:23][C:12]([CH2:24][N:25]4[CH2:26][CH2:27][C:28]([C:3]([CH3:6])([CH3:5])[CH3:4])([OH:31])[CH2:29][CH2:30]4)([C:13]4[C:18]3=[CH:17][CH:16]=[CH:15][CH:14]=4)[C:11]=2[CH:10]=1

Participants

5

Reactant 3

HCID 82050Lithium BromideHCID 214806221-(2-Chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)-4-piperidinoneHCID 178418306HCID 178418306, compound

Product 1

HCID 214806871-(2-Chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)-4-(1,1-dimethylethyl)piperidin-4-olYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled solution (-78° C.) of lithium bromide (770 mg, 8.87 mmol, 1.5 eq) in tetrahydrofuran (60 mL) under nitrogen was added recently titrated t-butyllithium (1.7M in pentane, 4.20 mL, 7.10 mmol, 1.2 eq). The resulting strong yellow color was quenched on the addition of a 1-(2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)-4-piperidinone (described in example 1m) (2.00 g, 5.92 mmol) solution in tetrahydrofuran (15 mL). The reaction was warmed to room temperature over 10 min and quenched with water (50 mL). The aqueous phase was extracted with ethyl acetate (3×60 mL). Combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated to an oil. The reaction mixture was purified by flash chromatography over silica gel (150 mL, eluent: 15% ethyl acetate in hexane) to obtain 1.22 g (52%) of the title compound as a white solid. TLC analysis (Rf 0.23, 20% ethyl acetate in hexane). 1H NMR (CDCl3, 300 MHz) 7.24 (m, 1H), 7.14 (m, 2H), 6.95 (m, 3H), 6.87 (m, 1H), 4.24 (br s, 1H), 3.56 (s, 2H), 2.82 (m, 2H), 2.59 (d, J=1.4 Hz, 2H), 2.50 (m, 2H), 1.74 (m, 2H), 1.50 (m, 2H), 0.91 (br s, 9H) MS (CI, CH4) m/z 396 (M+1,100), 398 (35), 424 (M+29,17), 378 (45), 360 (6) The free base was dissolved in diethyl ether containing a small amount of methylene chloride and acidified with ethereal HCl. The hydrochloride salt was filtered, washed with fresh ether and dried in vacuo (60° C., 13 pascal, 18 h) to yield a white solid, mp 294°-296° C.

Workup

  1. customquenched with water (50 mL)
  2. extractionThe aqueous phase was extracted with ethyl acetate (3×60 mL)
  3. dry with materialCombined organic extracts were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to an oil
  6. customThe reaction mixture was purified by flash chromatography over silica gel (150 mL, eluent: 15% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-c9936fc214b14aaa981a6f0b23edc459
Source dataset
uspto-grants-1997_10
Patent number
US05681840

Reaction notes

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