4-Methylmorpholine → HCID 178475081, compound

HRID 1106120Notes

Reaction equation

HRID 1106120 reaction equation
[C:1]([NH:4][C@@H:5]([C:9]([OH:11])=O)[CH:6]([CH3:8])[CH3:7])(=[O:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[N:39]=[C:38]([OH:40])[C:37]([C:41]([OH:43])=[O:42])=[CH:36][N:35]=2)=[CH:30][CH:29]=1.C(N(CC)CC)C>CN(C)C(=O)C.ClCCl>[C:1]([NH:4][C@@H:5]([C:9]([NH:27][C:28]1[CH:29]=[CH:30][C:31]([C:34]2[N:39]=[C:38]([OH:40])[C:37]([C:41]([OH:43])=[O:42])=[CH:36][N:35]=2)=[CH:32][CH:33]=1)=[O:11])[CH:6]([CH3:7])[CH3:8])(=[O:3])[CH3:2]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 76475N-Acetyl-D-valineHCID 178507442HCID 178507442, compound

Product 1

HCID 178475081HCID 178475081, compoundYield 49.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent

Procedure

A suspension of 11.41 g (71.7 mmol) of N-acetyl-D-valine and 150 ml of dichloromethane is stirred at room temperature and 7.9 ml (71.7 mmol) of N-methylmorpholine is added. The resulting solution is cooled to -10° C. and 9.3 ml (71.7 mmol) of isobutyl chloroformate is added. The reaction mixture is stirred at -15°±5° C. for 45 min and an ice cold solution of 11.09 g (48 mmol) of 2-(4-aminophenyl)-4-hydroxy-5-pyrimidine carboxylic acid, 7.4 ml (52.8 mmol) of triethylamine, and 200 ml of N,N-dimethylacetamide is added while keeping the temperature below -10° C. The mixture is stirred at 0°-5° C. for 2 hrs and overnight at room temperature. A small amount of solid is filtered and the filtrate is evaporated to dryness. Water is added to the residue and the resulting solid filtered, washed with water, ethyl acetate, and ether and dried to give 8.9 g of 2-[4-(N-acetyl-D-valylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid. A second crop, obtained from the aqueous filtrate, weighs 2.35 g. [α]D23 +4.50 (cl, pH 7).

Workup

  1. temperatureThe resulting solution is cooled to -10° C.
  2. stirringThe reaction mixture is stirred at -15°±5° C. for 45 min
  3. customthe temperature below -10° C
  4. stirringThe mixture is stirred at 0°-5° C. for 2 hrs and overnight at room temperature
  5. filtrationA small amount of solid is filtered
  6. customthe filtrate is evaporated to dryness
  7. additionWater is added to the residue
  8. filtrationthe resulting solid filtered
  9. washwashed with water, ethyl acetate, and ether
  10. customdried

Sources & evidence

ORD record
ord-e9b9f4b2eb5a45d9985549e91d7b8bdb
Source dataset
uspto-grants-1982_01
Patent number
US04311699

Reaction notes

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