Dichloromethane → 4-[3-(3-Benzyl-3,8-diazabicyclo[3.2.1]oct-8-yl)-2-hydroxypropoxy]benzonitrile

HRID 1743703Notes

Reaction equation

[CH2:1]([N:8]1[CH2:14][CH:13]2[NH:15][CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:16]1[CH2:18][CH:17]1[CH2:19][O:20][C:21]1[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][CH:22]=1.C(Cl)Cl>CC(O)C.O>[CH2:1]([N:8]1[CH2:14][CH:13]2[N:15]([CH2:18][CH:17]([OH:16])[CH2:19][O:20][C:21]3[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][CH:22]=3)[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 3-benzyl-3,8-diazabicyclo[3.2.1]octane (3.46 g, 17.1 mmol; from Preparation B, step (e) above) and 4-(2-oxiranylmethoxy)benzonitrile (3.00 g, 17.1 mmol; prepared as described in international patent application WO 99/31100) in 2-propanol (70 mL) and H2O (7 mL) was stirred at 60° C. for 22 h. The reaction mixture was concentrated in vacuo. The residue was dissolved in CH2Cl2 (200 mL) and washed with water (50 mL) and brine (50 mL). The organic layer was dried (NaSO4), filtered and concentrated in vacuo to give the crude product. Flash chromatography on silica gel eluting with CH2Cl2:CMA (8:1) gave 5.74 g (89%) of the sub-title compound as a yellow oil.

Workup

concentrationThe reaction mixture was concentrated in vacuo
dissolutionThe residue was dissolved in CH2Cl2 (200 mL)
washwashed with water (50 mL) and brine (50 mL)
dry with materialThe organic layer was dried (NaSO4)
filtrationfiltered
concentrationconcentrated in vacuo
customto give the crude product

Sources & evidence

ORD record: ord-22d5a7ff5b8b457da924a510e450c6b0
Source dataset: uspto-grants-2006_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07012074B2

Reaction notes

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