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

HRID 2278557Notes

Reaction equation

HRID 2278557 reaction equation
[F:1][CH2:2][CH:3]1[O:8][CH2:7][CH2:6][NH:5][CH2:4]1.[CH2:9]([O:11][C:12](=[O:23])[CH2:13][C:14]1[N:19]=[C:18](Cl)[CH:17]=[C:16]([O:21]C)[N:15]=1)[CH3:10].[Na+].[Cl-]>CS(C)=O.C(N(CC)CC)C>[CH2:9]([O:11][C:12](=[O:23])[CH2:13][C:14]1[NH:15][C:16](=[O:21])[CH:17]=[C:18]([N:5]2[CH2:6][CH2:7][O:8][CH:3]([CH2:2][F:1])[CH2:4]2)[N:19]=1)[CH3:10]

Participants

6

Reactant 3

HCID 5234Sodium ChlorideHCID 101031572-(Fluoromethyl)morpholineHCID 86699270Ethyl 2-(4-chloro-6-methoxypyrimidin-2-yl)acetate

Product 1

HCID 136378682(+/-)-[4-(2-Fluoromethylmorpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetic acid ethyl esterYield 50.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
85 °C

Procedure

In a 50 ml round-bottomed flask, 680 mg of 2-fluoromethylmorpholine (Yoshikazu Jinho et al.; J. Med. Chem., 37(17), 2791-2796; 1994) and 0.63 g of (4-chloro-6-methoxypyrimidin-2-yl)acetic acid ethyl ester (example 8b, step 2b) are placed in 15 ml of DMSO and 1,013 ml of triethylamine. The reaction medium is heated for 18 h at 85° C. The reaction medium is poured into a saturated NaCl solution and the mixture is extracted with 3 times 25 ml of ethyl acetate. The organic extracts are combined and washed with a saturated NaCl solution, dried over magnesium sulfate and evaporated. The compound obtained is chromatographed on silica gel (15-40 μm, Merck), elution being carried out with a gradient of dichloromethane and methanol (98/2 to 95/5 v/v). The fractions containing the expected compound are combined and evaporated, so as to give (±)-[4-(2-fluoromethylmorpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetic acid ethyl ester (412 mg).

Workup

  1. extractionthe mixture is extracted with 3 times 25 ml of ethyl acetate
  2. washwashed with a saturated NaCl solution
  3. dry with materialdried over magnesium sulfate
  4. customevaporated
  5. customThe compound obtained
  6. customis chromatographed on silica gel (15-40 μm, Merck), elution
  7. additionThe fractions containing the expected compound
  8. customevaporated

Sources & evidence

ORD record
ord-c35af7d1b7da41ec8d93772ca0579c49
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

Loading…