Lithium Hydroxide → 3-(Hydroxymethyl)-5-methoxybenzoic acid
Reaction equation
OCC1C=C(C=C(OC)C=1)C(NC1CCNCC1)=O.C[O:21][C:22](=[O:33])[C:23]1[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[C:25]([CH2:31][OH:32])[CH:24]=1.[Li+].[OH-]>C1COCC1.CO>[OH:32][CH2:31][C:25]1[CH:24]=[C:23]([CH:28]=[C:27]([O:29][CH3:30])[CH:26]=1)[C:22]([OH:33])=[O:21]Participants
Procedure
In analogy to the procedure described in example 50k), 3-hydroxymethyl-5-methoxy-N-piperidin-4-yl-benzamide [prepared by i) saponification of 3-hydroxymethyl-5-methoxy-benzoic acid methyl ester [Synthetic Communications, 31(12), 1921-1926; 2001] with LiOH in THF/MeOH (2:1) to give 3-hydroxymethyl-5-methoxy-benzoic acid in analogy to the procedure described in example 53; ii) subsequent condensation with 4-amino-piperidine-carboxylic acid tert-butyl ester to give 4-(3-hydroxymethyl-5-methoxy-benzoylamino)-piperidine-1-carboxylic acid tert-butyl ester, using N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride and N,N-dimethyl-4-aminopyridine in MeCl2 in analogy to the procedure described in example 60d); iii) Boc cleavage with TFA in analogy to the procedure described in example 50i)] was reacted with 3,5-diethoxy-4-fluoro-benzaldehyde (example 50 g), sodium cyanoborohydride, N-ethyl-diisopropylamine and acetic acid in ethanol at 50° C. to yield the title compound as off-white solid. MS: 461.1 (MH+).
Sources & evidence
- ORD record
- ord-a25ae29bc1fe4a0abd9deb45eaba557a
- Source dataset
- uspto-grants-2010_08
- Patent number
- US07772253B2
Reaction notes
Loading…