Methane → 6-(3-Chloro-4-fluorobenzoyl)-1-oxa-6-azaspiro[2.5]octane-2-carbonitrile

HRID 1272511Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[F:17])[C:5]([N:7]1[CH2:12][CH2:11][C:10](=[O:13])[CH2:9][CH2:8]1)=[O:6].Cl[CH2:19][C:20]#[N:21].C>ClCCl.[OH-].[Na+].[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[F:17])[C:5]([N:7]1[CH2:8][CH2:9][C:10]2([O:13][CH:19]2[C:20]#[N:21])[CH2:11][CH2:12]1)=[O:6]

Participants

Conditions

Temperature: 15 °C

Procedure

A suspension of 1-(3-chloro-4-fluorobenzoyl)piperidin-4-one (4160 g, 16.27 mol) in 28.4 liters of dichloromethane and 11.7 liters of sodium hydroxide at 30.5%, supplemented with 186 g of tetrabutylammonium chloride, is cooled to 15° C. Chloroacetonitrile (1540 ml, 24.4 mol) is then added slowly and with vigorous stirring and the mixture is stirred for 3 hours at 20° C. Further addition of chloroacetonitrile (500 ml) is carried out in order to complete the reaction. The reaction medium is diluted with dichloromethane (8.5 liters) and water (20 liters) and then separated by decantation and washed again with water. The brown solution obtained is decolorized with 2 kg of silica and 500 g of animal charcoal and then evaporated to dryness. The residue obtained is crystallized from isopropanol in order to give, after filtration, 3426 g of brown crystals. m.p.=100–101° C.

Workup

stirringthe mixture is stirred for 3 hours at 20° C
customthe reaction
customseparated by decantation
washwashed again with water
customThe brown solution obtained
customevaporated to dryness
customThe residue obtained
customis crystallized from isopropanol in order
customto give
filtrationafter filtration, 3426 g of brown crystals

Sources & evidence

ORD record: ord-da48c8f1b19f419eb41a2cb3005a31a4
Source dataset: uspto-grants-2007_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07208603B2

Reaction notes

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