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

HRID 707521Notes

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)[CH2:14][C@@H:13]3[CH3:25])[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])[CH2:14][C@@H:13]3[CH3:25])[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(3S)-4-(1-(diphenylmethyl)azetidin-3-yl)-3-methylpiperazine-1-carboxylate (493 mg, 1.17 mmol) described in Production Example 6-1 and THF (10.0 mL) was added lithium aluminum hydride (178 mg, 4.68 mmol) at 0° C. The resultant mixture was stirred under reflux for 5 hours and 10 minutes. The reaction mixture was cooled to 0° C., then water (178 μL) and a 5 N aqueous sodium hydroxide solution (178 μL) were added thereto, and water (534 μL) was further 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 (321 mg, yield: 82%).

Workup

temperatureunder reflux for 5 hours and 10 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-0895259e37e24000a4a736eb80f47529
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174998B2

Reaction notes

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