Sodium Chloride → [4-(2-Hydroxymethylmorpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetic acid ethyl ester

HRID 2278550Notes

Reaction equation

HRID 2278550 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[CH2:5][C:6]1[NH:7][C:8](=[O:13])[CH:9]=[C:10](Cl)[N:11]=1)[CH3:2].Cl.[NH:16]1[CH2:21][CH2:20][O:19][CH:18]([CH2:22][OH:23])[CH2:17]1.[Na+].[Cl-].C(Cl)Cl>CS(C)=O.C(N(CC)CC)C.C(OC(C)C)(C)C>[CH2:1]([O:3][C:4](=[O:14])[CH2:5][C:6]1[NH:7][C:8](=[O:13])[CH:9]=[C:10]([N:16]2[CH2:21][CH2:20][O:19][CH:18]([CH2:22][OH:23])[CH2:17]2)[N:11]=1)[CH3:2]

Participants

8

Reactant 4

HCID 5234Sodium ChlorideHCID 6344DichloromethaneHCID 19777263Morpholin-2-ylmethanol hydrochlorideHCID 136378677Ethyl 2-(6-chloro-4-oxo-1,4-dihydropyrimidin-2-yl)acetate

Product 1

HCID 136378679[4-(2-Hydroxymethylmorpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetic acid ethyl esterYield 14%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 7914Diisopropyl EtherSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
85 °C

Procedure

Under argon, in a 500 ml round-bottomed flask equipped with a thermometer and a condenser, 10 g of (4-chloro-6-oxo-1,6-dihydropyrimidin-2-yl)acetic acid ethyl ester (example 25b, step 5b) and 9.6 g of morpholin-2-yl-methanol hydrochloride obtained previously are successively placed in 200 ml of DMSO and 16.1 ml of triethylamine. The reaction medium is heated for 22 h at 85° C. After returning to ambient temperature (20° C.), the reaction medium is poured into a saturated NaCl solution, and the mixture is extracted with 8×250 ml of ethyl acetate. The organic extracts are combined, dried over magnesium sulfate, filtered, and evaporated under reduced pressure. A solid is obtained which is slurried in diisopropyl ether containing 10% of methylene chloride. The solid is filtered off, and rinsed twice and then once with pentane. [4-(2-Hydroxymethylmorpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetic acid ethyl ester is isolated (1.9 g; yield=14%) in the form of a beige solid.

Workup

  1. customobtained previously
  2. customAfter returning to ambient temperature
  3. custom(20° C.)
  4. extractionthe mixture is extracted with 8×250 ml of ethyl acetate
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customA solid is obtained which
  9. filtrationThe solid is filtered off
  10. washrinsed twice

Sources & evidence

ORD record
ord-7e4def9c85e048c18b2ba576db104ce2
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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