Acetic Acid → 4-(6-Hexanamido-2,3-dihydrobenz-1,4-oxazin-4-ylmethyl)-3-hydroxybenzoic acid

HRID 1080795Notes

Reaction equation

HRID 1080795 reaction equation
C([Li:5])CCC.[CH2:6]([SH:8])[CH3:7].[C:9]([NH:16][C:17]1[CH:18]=[CH:19][C:20]2[O:25][CH2:24][CH2:23][N:22]([CH2:26][C:27]3[CH:36]=[CH:35][C:30]([C:31]([O:33]C)=[O:32])=[CH:29][C:28]=3[O:37]C)[C:21]=2[CH:39]=1)(=[O:15])[CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].C(O)(=O)C>CN1C(=O)N(C)CCC1.O>[S-:8][CH2:6][CH3:7].[Li+:5].[C:9]([NH:16][C:17]1[CH:18]=[CH:19][C:20]2[O:25][CH2:24][CH2:23][N:22]([CH2:26][C:27]3[CH:36]=[CH:35][C:30]([C:31]([OH:33])=[O:32])=[CH:29][C:28]=3[OH:37])[C:21]=2[CH:39]=1)(=[O:15])[CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 6343EthanethiolHCID 23365905Methyl 4-(6-hexanamido-2,3-dihydrobenz-1,4-oxazin-4ylmethyl)-3-methoxybenzoateHCID 178418339Butyllithium

Product 2

HCID 10866251Lithium thioethoxideHCID 233658934-(6-Hexanamido-2,3-dihydrobenz-1,4-oxazin-4-ylmethyl)-3-hydroxybenzoic acidYield 36%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent2×

Procedure

Lithium thioethoxide was prepared by the dropwise addition of n-butyllithium (4 ml. of 1.53 molar solution in hexane) to a stirred solution of ethyl mercaptan (0.5 ml.) in dry N,N'-dimethylpropylene urea (DMPU) (9 ml.), under a nitrogen atmosphere. A solution of methyl 4-(6-hexanamido-2,3-dihydrobenz-1,4-oxazin-4-ylmethyl)-3-methoxybenzoate (prepared as described in Example 26) (0.35 g.) in DMPU (3 ml.) was added, the mixture stirred at ambient temperature for 15 minutes, then heated to, and maintained at, 130° C. for 4 hours. The cooled mixture was diluted with water, acidified with acetic acid, extracted with ethyl acetate, the extracts washed with water, dried (MgSO4) and evaporated. The product was purified by flash chromatography on silica gel, eluting with 80:20:2 v/v/v toluene:ethyl acetate:acetic acid, giving a white solid which was washed with hexane and dried, to give the title compound (0.114 g., 36%) as a white solid, m.p. 183°-184° C.

Workup

  1. temperatureheated to, and
  2. temperaturemaintained at, 130° C. for 4 hours
  3. extractionextracted with ethyl acetate
  4. washthe extracts washed with water
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe product was purified by flash chromatography on silica gel
  8. washeluting with 80:20:2 v/v/v toluene
  9. customethyl acetate:acetic acid, giving a white solid which
  10. washwas washed with hexane
  11. customdried

Sources & evidence

ORD record
ord-dc805ebde1554098aa7cd4b4881f3ac5
Source dataset
uspto-grants-1996_12
Patent number
US05583152

Reaction notes

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