Cyclopropylamine → N-(3,3-bis(4-fluorophenyl)propyl)cyclopropanamine

HRID 2190350Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH2:9][CH:10]=O)=[CH:4][CH:3]=1.[CH:19]1([NH2:22])[CH2:21][CH2:20]1.[BH4-].[Na+]>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH2:9][CH2:10][NH:22][CH:19]2[CH2:21][CH2:20]2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 25 °C

Procedure

To solution of 3,3-bis(4-fluorophenyl)propanal (1.00 g, 4.06 mmol, see Method H for preparation) in MeOH (15 ml) was added cyclopropanamine (0.285 ml, 4.06 mmol). The reaction mixture was stirred for overnight at 25° C. Sodium borohydride (0.307 g, 8.12 mmol) was carefully added to the reaction mixture over 15 min. After stirring an additional 15 min volatiles were removed by concentration under reduced pressure. The leftover residue was solubilized with 60 mL of a 1:2 mixture of 10% NaOH and ethyl acetate. The organic phase was separated and the aqueous phase was extracted further with ethyl acetate (2×40 mL). Purification by chromatography on silica (eluted with 0->10% MeOH/CH2Cl2+0->1% NH4OH) gave N-(3,3-bis(4-fluorophenyl)propyl)cyclopropanamine 181. The product was dissolved in CH2Cl2 and made into the HCl salt by precipitation with etheral HCl and then concentration of volatiles.

Workup

stirringAfter stirring an additional 15 min volatiles
customwere removed by concentration under reduced pressure
additionThe leftover residue was solubilized with 60 mL of a 1:2 mixture of 10% NaOH and ethyl acetate
customThe organic phase was separated
extractionthe aqueous phase was extracted further with ethyl acetate (2×40 mL)
customPurification by chromatography on silica (eluted with 0->10% MeOH/CH2Cl2+0->1% NH4OH)

Sources & evidence

ORD record: ord-6c5cd7f7ce3642f7be43918c7b506a45
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08324396B2

Reaction notes

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