Ammonium Chloride → 8-bromo-1,4-dioxaspiro[4.5]decane

HRID 727148Notes

Reaction equation

HRID 727148 reaction equation
[Br:1][CH:2]1[CH2:11][CH2:10][C:5]2([O:9][CH2:8][CH2:7][O:6]2)[CH2:4][CH2:3]1.FC(F)(F)[C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH:17]=[O:18].[Cl-].[NH4+]>>[Br:1][CH:2]1[CH2:11][CH2:10][C:5]2([O:6][CH2:7][CH2:8][O:9]2)[CH2:4][CH2:3]1.[O:9]1[C:5]2([CH2:10][CH2:11][CH:2]([C:15]3[CH:14]=[CH:21][CH:20]=[CH:19][C:16]=3[CH2:17][OH:18])[CH2:3][CH2:4]2)[O:6][CH2:7][CH2:8]1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 679903-(Trifluoromethyl)benzaldehydeHCID 137651298-bromo-1,4-dioxaspiro[4.5]decane

Product 2

HCID 137651298-bromo-1,4-dioxaspiro[4.5]decaneHCID 19705209HCID 19705209, compound

Procedure

When the bridging group is carbonyl, the Grignard reagent of 8-bromo-1,4-dioxaspiro[4.5]decane is first prepared. The precursor 8-bromo-1,4-dioxaspiro[4.5]decane is prepared by the method of E. I. Snyder (JOC, 36, 403 (1971)). The Grignard reagent is in turn reacted with an appropriately substituted or unsubstituted benzaldehyde, for example, 3-trifluoromethylbenzaldehyde and then treated with aqueous ammonium chloride, yielding [(1,4-dioxaspiro[4.5]decan-8-yl)(phenyl)]methanol. The so-prepared alcohol is treated with sodium hydride in toluene, and then is reacted with phenylmethyl bromide, yielding phenylmethyl [(1,4-dioxaspiro[4.5]decan-8-yl)(phenyl)]methyl ether. The 1,4-dioxaspiro functional group is then cleaved from the so-prepared molecule with acetic acid and water, as previously described, affording the corresponding phenylmethyl [(cyclohexanon-4-yl)(phenyl)]methyl ether. The ether is then reacted with cyanoguanidine, as previously described, yielding the appropriate 2,4-diamino-6-[(phenylmethoxy)(phenyl)methyl]-5,6,7,8-tetrahydroquinazoline. The tetrahydroquinazoline is then cleaved with hydrogen gas in the presence of 5% palladium on charcoal, yielding the corresponding [(2,4-diamino-5,6,7,8-tetrahydroquinazolin-6-yl)(phenyl)]methanol. Using the method of D. Swern (Tetrahedron, 34, 1651-1660 (1978)), the methanol is oxidized with oxalyl chloride and dimethyl sulfoxide in methylene chloride, yielding the targeted 2,4-diamino-6-phenylcarbonyl-5,6,7,8-tetrahydroquinazoline. Example 9 provides a detailed description of how this reaction is conducted.

Sources & evidence

ORD record
ord-85cb825e1a75472698e536b98dbe93d2
Source dataset
uspto-grants-1998_01
Patent number
US05712281

Reaction notes

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