Tetrahydrofuran → (2R)-4-(1-(Diphenylmethyl)azetidin-3-yl)-1,2-dimethylpiperazine

HRID 707517Notes

Reaction equation

[C:1]1([CH:7]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:8]2[CH2:11][CH:10]([N:12]3[CH2:17][CH2:16][N:15]([C:18](OC(C)(C)C)=O)[C@H:14]([CH3:25])[CH2:13]3)[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1COCC1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>O>[C:26]1([CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:8]2[CH2:11][CH:10]([N:12]3[CH2:17][CH2:16][N:15]([CH3:18])[C@H:14]([CH3:25])[CH2:13]3)[CH2:9]2)[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a mixed solution of tert-butyl(2R)-4-(1-(diphenylmethyl)azetidin-3-yl)-2-methylpiperazine-1-carboxylate (476 mg, 1.13 mmol) described in Production Example 5-1 and THF (10.0 mL) was added lithium aluminum hydride (171 mg, 4.52 mmol) at 0° C., and the resultant mixture was stirred under reflux for 1 hour and 55 minutes. The reaction mixture was cooled to 0° C., water (171 μL) and a 5 N aqueous sodium hydroxide solution (171 μL) were added thereto, and water (513 μL) was additionally added thereto. The reaction mixture was filtrated using Celite and then washed with ethyl acetate. A filtrate was concentrated under a reduced pressure and the resultant residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=2:1) to give the title compound (342 mg, yield: 90%).

Workup

temperatureunder reflux for 1 hour and 55 minutes
filtrationThe reaction mixture was filtrated
washwashed with ethyl acetate
concentrationA filtrate was concentrated under a reduced pressure
customthe resultant residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=2:1)

Sources & evidence

ORD record: ord-ddcf8da73d564178b6febb0b2e82c389
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174998B2

Reaction notes

Loading…