Bromocyclopentane → HCID 59837486, compound

HRID 272996Notes

Reaction equation

HRID 272996 reaction equation
[CH:1]1(Br)[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].[NH:9]1[CH2:12][CH:11]([CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3([CH2:27][N:28]([CH3:30])[CH3:29])[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:17][CH:16]=2)[CH2:10]1>CC(C)=O>[CH:1]1([N:9]2[CH2:12][CH:11]([CH2:13][O:14][C:15]3[CH:16]=[CH:17][C:18]([C:21]4([CH2:27][N:28]([CH3:30])[CH3:29])[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)=[CH:19][CH:20]=3)[CH2:10]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 8728BromocyclopentaneHCID 14798Sodium HydroxideHCID 68577529HCID 68577529, compound

Product 1

HCID 59837486HCID 59837486, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Cyclopentyl bromide (0.17 ml, 1.54 mmol) and 5M aqueous sodium hydroxide (0.34 ml, 1.68 mmol) were added to a solution of 1-{4-[4-(azetidin-3-ylmethoxy)phenyl]tetrahydro-2H-pyran-4-yl]-N,N-dimethylmethanamine (425 mg, 1.4 mmol) in acetone (9 ml). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated in vacuo. The residue was taken up in 2N hydrochloric acid to reach pH 1 and extracted with tert-butylmethyl ether (2×15 ml). The aqueous layer was then basified to pH14 with 4M sodium hydroxide (ca 40 ml) and extracted with dichloromethane (3×30 ml). These organic layers were combined, dried over magnesium sulphate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:4:1 by volume) to provide the title compound (55 mg, 11%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 1.28-1.73 (m, 8H), 1.83-1.93 (m, 2H), 1.96 (s, 6H), 2.05-2.13 (m, 2H), 2.40 (s, 2H), 2.71 (m, 1H), 2.90 (m, 1H), 3.00 (t, 2H), 3.39-3.58 (m, 4H), 3.72-3.78 (m, 2H), 4.05 (d, 2H), 6.87 (d, 2H), 7.21 (d, 2H). LRMS ESI+ m/z 373 [MH]+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. extractionextracted with tert-butylmethyl ether (2×15 ml)
  3. extractionextracted with dichloromethane (3×30 ml)
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:4:1 by volume)

Sources & evidence

ORD record
ord-1d003e396ef045558a11c110599cb989
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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