phosphenous acid → 3(s)-(4-Chloro-phenyl)-2(s)-ethyl-n-hydroxy-4-morpholin-4-yl-4-oxo-butyramide

HRID 733320Notes

Reaction equation

HRID 733320 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:15]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[O:16])[C@H:9]([CH2:13][CH3:14])[C:10](O)=[O:11])=[CH:4][CH:3]=1.OP=O.[Si]([O:30][NH2:31])(C)(C)C>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:15]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[O:16])[C@H:9]([CH2:13][CH3:14])[C:10]([NH:31][OH:30])=[O:11])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 22497phosphenous acidHCID 2734666O-(Trimethylsilyl)hydroxylamine2×HCID 113133743(S)-(4-Chloro-phenyl)-2(S)-ethyl-4-morpholin-4-yl-4-oxo-butyric acid

Product 1

HCID 99279313(s)-(4-Chloro-phenyl)-2(s)-ethyl-n-hydroxy-4-morpholin-4-yl-4-oxo-butyramide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The crude acid 1b (310 mg, 0.95 mmol) was dissolved in 5 ml of dichloromethane. HOPO (111 mg, 1 mmol) and MEI (0.159 ml, 1.14 mmol) were added successively. The mixture was stirred for 30 minutes, then TMSONH2 (0.233 ml, 1.9 mmol) was added. After one hour another portion of TMSONH2 (0.233 ml, 1.9 mmol) was added and stirring continued over night. The reaction mixture was filtered (solid contained mostly HOPO) diluted with 20 ml of dichloromethane and extracted twice with 2N-HCl and brine, dried over anhydrous sodium sulfate and evaporated. The crude solid (237 mg, 73%) was purified by preparative HPLC (methanol/water=1/1). Yield: 100 mg (31%).

Workup

  1. stirringstirring
  2. waitcontinued over night
  3. filtrationThe reaction mixture was filtered (solid
  4. additiondiluted with 20 ml of dichloromethane
  5. extractionextracted twice with 2N-HCl and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated
  8. customThe crude solid (237 mg, 73%) was purified by preparative HPLC (methanol/water=1/1)

Sources & evidence

ORD record
ord-d2f47feed4234b039e031033850dfaa3
Source dataset
uspto-grants-2009_09
Patent number
US07589091B2

Reaction notes

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