1,4-Dioxa-8-aza-spiro[4.5]decane-8-carbonitrile → 8-(3-Phenyl-1,2,4-oxadiazol-5-yl)-1,4-dioxa-8-azaspiro[4.5]decane

HRID 1409686Notes

Reaction equation

[OH:1][NH:2][C:3](=[NH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[O:11]1[C:15]2([CH2:20][CH2:19][N:18]([C:21]#N)[CH2:17][CH2:16]2)[O:14][CH2:13][CH2:12]1>O1CCCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[C:4]1([C:3]2[N:10]=[C:21]([N:18]3[CH2:19][CH2:20][C:15]4([O:11][CH2:12][CH2:13][O:14]4)[CH2:16][CH2:17]3)[O:1][N:2]=2)[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A 0.5 M solution of zinc chloride in tetrahydrofuran (18.00 mL) is added dropwise at room temperature to a mixture of N-hydroxy-benzamidine (817 mg) and 1,4-dioxa-8-aza-spiro[4.5]decane-8-carbonitrile (1.00 g) in ethyl acetate (20 mL). The reaction mixture is stirred at 50° C. for 3 h and cooled to room temperature. The precipitate is filtered off and heated to 100° C. for 1 h in a mixture of ethanol (10 mL) and glacial acetic acid (5 mL). The solvents are evaporated and the crude product is purified by HPLC. TLC: rf=0.88 (silica gel, CH2Cl2/MeOH 9:1); Mass spectrum (ESI+): m/z=288 [M+H]+.

Workup

temperaturecooled to room temperature
filtrationThe precipitate is filtered off
temperatureheated to 100° C. for 1 h in a mixture of ethanol (10 mL) and glacial acetic acid (5 mL)
customThe solvents are evaporated
customthe crude product is purified by HPLC

Sources & evidence

ORD record: ord-feeabd061c654b16aa05ad1ff24bc246
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921398B2

Reaction notes

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