4-Methylmorpholine → HCID 15521370, compound

HRID 1978214Notes

Reaction equation

HRID 1978214 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([CH2:12][CH:13]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:14](O)=[O:15])(=[O:11])=[O:10])=[CH:5][CH:4]=1.CN1CCOCC1.ClC(OCC)=O.Cl.[CH2:38]([O:45][NH2:46])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C1COCC1>[CH2:38]([O:45][NH:46][C:14](=[O:15])[CH:13]([CH2:12][S:9]([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)(=[O:10])=[O:11])[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 10928Ethyl chloroformateHCID 102312Benzyloxyamine hydrochlorideHCID 15521369HCID 15521369, compound

Product 1

HCID 15521370HCID 15521370, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 2-[(4-methoxybenzenesulfonyl)methyl]-3-phenyl-propionic acid (1.05 g, 3.14 mmol) and 0.69 mL (6.3 mmol) of NMM in dry THF, under nitrogen, is cooled in an ice bath. Ethyl chloroformate (0.33 mL, 3.5 mmol) in 7 mL of THF is added dropwise over 5 minutes. The suspension is stirred at 0° C. for 10 minutes, after which a slurry of O-benzylhydroxylamine hydrochloride (0.64 g, 4 mmol) and NMM (0.44 mL, 4 mmol) in 7 mL of THF is introduced in several portions. The mixture is stirred for 10 minutes and stored at 10° C. overnight. The mixture is allowed to warm to room temperature for 0.5 hours, and is then partitioned between ethyl acetate and aqueous 10% HCl. The organic phase is washed with water, three portions of 1M sodium bicarbonate and brine. It is dried over anhydrous sodium sulfate, concentrated and chromatographed on silica gel, eluting with 40%-50% ethyl acetate in hexanes. This affords 1.26 g of the title compound as a colorless oil.

Workup

  1. stirringThe mixture is stirred for 10 minutes
  2. waitstored at 10° C. overnight
  3. temperatureto warm to room temperature for 0.5 hours
  4. customis then partitioned between ethyl acetate and aqueous 10% HCl
  5. washThe organic phase is washed with water, three portions of 1M sodium bicarbonate and brine
  6. dry with materialIt is dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customchromatographed on silica gel
  9. washeluting with 40%-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-f4f6cc8490834682bc735d6031171650
Source dataset
uspto-grants-2001_05
Patent number
US06235928B1

Reaction notes

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