Morpholine → 2-Ethylsulfanyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid

HRID 1753849Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([S:8][CH2:9][CH3:10])[C:5]([C:11]([OH:13])=[O:12])=[C:4]([CH3:14])[CH:3]=1.[NH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1>[OH-].[Na+]>[CH2:9]([S:8][C:6]1[C:5]([C:11]([OH:13])=[O:12])=[C:4]([CH3:14])[CH:3]=[C:2]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:7]=1)[CH3:10]

Participants

Conditions

Temperature: 105 °C

Procedure

A mixture of 12.0 g (51.7 mmol) 6-chloro-2-ethylsulfanyl-4-methyl-pyridine-3-carboxylic acid and 33.7 g (387 mmol) morpholine was heated to 105° C. for 5 d. After cooling to RT a 2M aq. NaOH sol. (200 ml) was added, followed by washing with ether (3×200 ml). The aqueous layer was then acidified with a 2M aq. HCl to pH 5 and extracted with EtOAc. In the same manner pH 4 was adjusted followed by extraction with EtOAc. The combined EtOAc extracts were dried over MgSO4 and concentrated in vacuo. Crystallisation (DCM/hexane) of the residue yielded 7.2 g (25.3 mmol, 49%) 2-ethylsulfanyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid.

Workup

additionwas added
washby washing with ether (3×200 ml)
extractionextracted with EtOAc
extractionIn the same manner pH 4 was adjusted followed by extraction with EtOAc
dry with materialThe combined EtOAc extracts were dried over MgSO4
concentrationconcentrated in vacuo
customCrystallisation (DCM/hexane) of the residue

Sources & evidence

ORD record: ord-e55995ea79ab41abb8a85baec891afa8
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09168259B2

Reaction notes

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