Formaldehyde → HCID 18700442, compound

HRID 2288979Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:22])[CH2:9][NH:10][C:11]([CH:13]2[CH2:18][CH2:17][N:16]([CH2:19][C:20]#[N:21])[CH2:15][CH2:14]2)=[O:12])=[CH:4][CH:3]=1.O.[C:24](=O)(O)[O-:25].[Na+].C=O>C(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:22])[CH:9]([NH:10][C:11]([CH:13]2[CH2:14][CH2:15][N:16]([CH2:19][C:20]#[N:21])[CH2:17][CH2:18]2)=[O:12])[CH2:24][OH:25])=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 40 °C

Procedure

In a 22-l round bottomed flask, suspend 1-cyanomethyl-piperidine-4-carboxylic acid-[2-(4-fluorophenyl)-2-oxoethyl] amide (1.004 kg, 3.31 moles) in absolute ethanol (5.0 l) and process water (2.5 l). To the suspension is added sodium bicarbonate (55.62 g, 0.662 moles) and 37% formaldehyde (400 ml, 4.93 moles), then the suspension is warmed to 40° C. and the reaction followed by HPLC. Upon completion, the reaction is quenched by added ice water (5.0 l) and brine (5.0 l). The reaction is stirred for three hours, then the crystals are collected by vacuum filtration, washed with process water (1.0 l) and dried at ambient temperature and 25 in Hg to give 1-cyanomethyl-piperidine-4-carboxylic acid-[2-(4-fluorophenyl)-1-hydroxymethyl-2-oxoethyl] amide (839 g, 2.52 moles). 1H NMR (400 MHz, d6 DMSO) d 1.52 (m, 2H), 1.67 (t, 2H), 2.12 (t, 2H), 2.23 (m, 1H), 2.77 (m, 2H), 3.38 (s, 1H), 3.65 (m, 1H), 3.68 (s, 2H), 3.75 (m, 1H), 5.15 (m, 1H), 5.25 (m, 1H), 7.16 (t, 2H), 8.06 (q, 2H), 8.40 (d, 1H).

Workup

customIn a 22-l round bottomed flask, suspend
customUpon completion, the reaction is quenched
additionby added ice water (5.0 l) and brine (5.0 l)
filtrationthe crystals are collected by vacuum filtration
washwashed with process water (1.0 l)
customdried at ambient temperature

Sources & evidence

ORD record: ord-dc48870c5fa946b8a4a8b3dd16c76b88
Source dataset: uspto-grants-2000_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06090825

Reaction notes

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