Hydrochloric Acid → HCID 53951462, compound

HRID 615351Notes

Reaction equation

HRID 615351 reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][S:9][CH:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[OH:17])[N:7]1[C:18](=[O:24])[CH2:19][CH2:20][C:21](O)=[O:22])=[O:5])[CH3:2].CN1CCOCC1.[NH2:32][OH:33].Cl>O1CCCC1.ClC(OCC(C)C)=O.CO>[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][S:9][CH:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[OH:17])[N:7]1[C:18](=[O:24])[CH2:19][CH2:20][C:21](=[O:22])[NH:32][OH:33])=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 79724-MethylmorpholineHCID 12837200HCID 12837200, compound2×

Product 1

HCID 53951462HCID 53951462, compoundYield 63.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 62365Isobutyl chloroformateSolvent

Procedure

To a stirred solution of (4R)-3-(3-carboxypropanoyl)-2-(2-hydroxyphenyl)-4-thiazolidinecarboxylic acid ethyl ester (compound 8a) (1.06 g) and N-methylmorpholine (0.33 ml) in 20 ml of anhydrous tetrahydrofuran, isobutyl chloroformate (0.39 ml) was added dropwise at -15° C., and stirred for additional 2 hours at this temperature. To this solution, the methanol solution of hydroxylamine (0.3 g) was added dropwise at -50° C. The reaction mixture was stirred for 1 hour at room temperature, acidified with N hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The residual oil was purified by silica gel column chlromatography to give 0.7 g (63%) of the titled compound. IR (KBr, cm-1) 3220, 1727, 1625, 1595, 1200, 1092, 753. NMR (acetone-d6, δ): 1.24 (3H, t, J=7.5 Hz, CO2CH2CH3), 2.17-3.07 (4H, m, CO--CH2)2CO), 3.30 (1H, ABq (A part), d, J=10.0, 2.0 Hz, C5 --HA), 3.47 (1H, ABq (B part), d, J=10.0, 7.0 Hz, C5 --HB), 4.14 (2H, q, J=7.5 Hz, CO2CH2), 5.18 (1H, dd, J=2.0, 7.0 Hz, C4 --H), 6.40 (1H, S, C2 --H), 6.88-7.27 (4H, m, arom. H), 8.60 (2H, br. s, NHOH), 9.77 (1H, br. s, OH )

Workup

  1. stirringThe reaction mixture was stirred for 1 hour at room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residual oil was purified by silica gel column chlromatography

Sources & evidence

ORD record
ord-d8d99818c90d4a5faee76caced58f9be
Source dataset
uspto-grants-1985_02
Patent number
US04499102

Reaction notes

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