3-Methoxybenzaldehyde → Ethyl 4-(3-methoxyphenyl)piperidine-3-carboxylate

HRID 1903356Notes

Reaction equation

HRID 1903356 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]2[CH2:14][CH2:13][N:12](C)[CH2:11][CH:10]2[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:6]=[CH:7][CH:8]=1.COC1C=C(C=CC=1)C=O.F[B-](F)(F)F.C[O+](C)C.[BH4-].[Na+]>C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH:10]2[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 115693-MethoxybenzaldehydeHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 4311764Sodium borohydrideHCID 12947549Ethyl 4-(3-methoxyphenyl)-1-methylpiperidine-3-carboxylate

Product 1

HCID 12947548Ethyl 4-(3-methoxyphenyl)piperidine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

In the preparation of ethyl 4-(3'-methoxyphenyl)-1-methylpiperidine-3-carboxylate (23), a synthesis of 4-aryl 2-unsubstituted nipecotic acids was developed. In this process modifying a known procedure [cf. C. F. Koelsch, J. of the Am. Chem. Soc., 65:2459 (1943)], 3-methoxybenzaldehyde (18) was converted to the amide ester, ethyl 4-(3'-methoxyphenyl)-2-piperidone-5-carboxylate (21), via standard procedures. Selective reduction of the amide function of 21 was achieved by reaction with trimethyloxonium fluoroborate followed immediately by treatment with NaBH4 in ethanol to yield amino ester, ethyl 4-(3'-methoxyphenyl)piperidine-3-carboxylate (22). Reductive methylation gave the required nipecotate 23 in 48% overall yield from 3-methoxybenzaldehyde (18).

Sources & evidence

ORD record
ord-95233504f17245d787f517ab316a89b8
Source dataset
uspto-grants-1984_03
Patent number
US04435572

Reaction notes

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