4-(Methoxymethylcarbamoyl)piperidine-1-carboxylic acid tert-butyl ester → N-Boc-(2,3-dimethoxyphenyl)-4-piperidinylmethanone

HRID 2055872Notes

Reaction equation

COCN[C:5]([CH:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1)=[O:6].[C:20]1([O:28][CH3:29])[C:21](=[CH:24][CH:25]=[CH:26][CH:27]=1)[O:22][CH3:23].O1CCCC1>O1CCCC1>[CH3:23][O:22][C:21]1[C:20]([O:28][CH3:29])=[CH:27][CH:26]=[CH:25][C:24]=1[C:5]([CH:7]1[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[CH2:11][CH2:12]1)=[O:6]

Participants

Conditions

Temperature: -17 °C

Procedure

Into a 500-mL jacketed-bottom-drain resin pot fitted with a five-joint head equipped with a mechanical stirrer, a thermocouple, a reflux condenser topped with a nitrogen bubbler, a septum, and a stopper was placed 28.9 g (0.092 mol) of 4-[(methoxymethylamino)carbonyl]-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester (15) (28.9 g, 0.092 mol, 87% pure) and 80 g of tetrahydrofuran. The solution was cooled to −17° C. and the cold lithiated veratrole/tetrahydrofuran slurry was added via cannula while maintaining the internal reaction temperature below −10° C. (15 minutes addition). The reaction mixture was then warmed to 10° C. and stirred for 3 hours. The solution may be used directly in Scheme L, step a, Example 109.

Workup

customequipped with a mechanical stirrer
temperaturewhile maintaining
additionthe internal reaction temperature below −10° C. (15 minutes addition)
temperatureThe reaction mixture was then warmed to 10° C.

Sources & evidence

ORD record: ord-46a539ac78ed4534822d275eae049432
Source dataset: uspto-grants-2008_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07332607B2

Reaction notes

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