Water ethanol → 1-[(S)-4-(2,3-Dihydro-[1,4]dioxino[2,3-b]pyridin-3-yl)-benzyl]-piperidine-4-carboxylic acid

HRID 1841973Notes

Reaction equation

HRID 1841973 reaction equation
[O:1]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[O:4][C@@H:3]([C:11]2[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=2)[CH2:2]1.[CH3:19][CH2:20][OH:21].[OH2:22]>>[O:1]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[O:4][C@@H:3]([C:11]2[CH:18]=[CH:17][C:14]([CH2:15][N:6]3[CH2:7][CH2:8][CH:19]([C:20]([OH:22])=[O:21])[CH2:10][CH2:5]3)=[CH:13][CH:12]=2)[CH2:2]1

Participants

3

Reactant 2

HCID 19096565Water ethanolHCID 86696106(S)-4-(2,3-Dihydro-[1,4]dioxino[2,3-b]pyridin-3-yl)-benzaldehyde2×

Product 1

HCID 683590441-[(S)-4-(2,3-Dihydro-[1,4]dioxino[2,3-b]pyridin-3-yl)-benzyl]-piperidine-4-carboxylic acid

Conditions

Temperature
25 °C

Procedure

To a solution of 1-[(8)-4-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-3-yl)-benzyl]-piperidine-4-carboxylic acid ethyl ester (prepared from Intermediate C and piperidine-4-carboxylic acid ethyl ester according to General Method F) (3.00 g, 7.90 mmol) in 4:1 EtOH/water (80 mL) is added LiOH monohydrate (0.994 g, 23.7 mmol) and the reaction stirred overnight at about 25° C. The reaction is concentrated, diluted with water and washed with Et2O (2×). The aqueous layer is lypholized to dryness then purified by silica gel chromatography eluting with 20% (2M NH3 in MeOH)/DCM. The pooled fractions are concentrated and dried to provide the title compound (K) as a foamed solid.

Workup

  1. concentrationThe reaction is concentrated
  2. additiondiluted with water
  3. washwashed with Et2O (2×)
  4. customthen purified by silica gel chromatography
  5. washeluting with 20% (2M NH3 in MeOH)/DCM
  6. concentrationThe pooled fractions are concentrated
  7. customdried

Sources & evidence

ORD record
ord-3ac42f74dabf4ea391d037e86f9d3454
Source dataset
uspto-grants-2015_02
Patent number
US08946203B2

Reaction notes

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