Oxalyl chloride → HCID 54202635, compound

HRID 1107148Notes

Reaction equation

HRID 1107148 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([S:11][C@H:12]([CH2:18][CH2:19][CH2:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C@H:13]([CH3:17])[C:14](O)=[O:15])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].C(Cl)(=O)C(Cl)=O.C[Si](C)(C)[O:36][NH2:37]>C(Cl)Cl>[OH:36][NH:37][C:14](=[O:15])[C@@H:13]([CH3:17])[C@H:12]([S:11][C:5]1[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=1)[CH2:18][CH2:19][CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 65578Oxalyl chlorideHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 54182937HCID 54182937, compound

Product 1

HCID 54202635HCID 54202635, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

(2R,3R)-3-(3,4-Dimethoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid (0.33 g, 0.85 mmol) is dissolved in CH2Cl2 (4 mL) and cooled to 0° C. and to this is added 2 M oxalyl chloride in CH2Cl2 (1.3 mL, 2.6 mmol) over 3 minutes. After 10 minutes the ice bath is removed and the reaction is stirred at room temperature for 2 hours. The reaction is concentrated in vacuo and azeotroped with chloroform twice. The residue is dissolved in CH2Cl2 (4 mL), cooled in ice and O-trimethylsilylhydroxylamine (0.32 mL, 2.6 mmol) is added over 2 minutes. After 10 minutes the reaction is concentrated in vacuo. The residue is dissolved in CH2Cl2 (50 mL) and washed with 1 N HCl (20 mL). The organic layer is dried over MgSO4 and the solvent removed in vacuo to give (+)-(2R,3R)-3-(3,4-Dimethoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid hydroxyamide (0.27 g, 79%): [a]D23 +40° (c=1.0, CHCl3); 1H NMR (300 MHz, CD3OD) δ 7.25-7.20 (m, 2H), 7.13-7.11 (m, 3H), 7.00-6.96 (m, 2H), 6.88 (d, J=8.0 Hz, 1H), 3.81 (s, 3H), 3.78 (s, 3H), 3.01-2.95 (m, 1H), 2.57-2.55 (m,1H), 2.23-2.15 (m, 1H), 1.71-1.41 (m, 6H), 1.34 (d, J=6.9 Hz, 3H); MS (FAB) m/e 404 (M+H)+.

Workup

  1. customAfter 10 minutes the ice bath is removed
  2. concentrationThe reaction is concentrated in vacuo
  3. customazeotroped with chloroform twice
  4. dissolutionThe residue is dissolved in CH2Cl2 (4 mL)
  5. temperaturecooled in ice
  6. concentrationAfter 10 minutes the reaction is concentrated in vacuo
  7. dissolutionThe residue is dissolved in CH2Cl2 (50 mL)
  8. washwashed with 1 N HCl (20 mL)
  9. dry with materialThe organic layer is dried over MgSO4
  10. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-d5675731a0984abcb97e1247689cb754
Source dataset
uspto-grants-2000_05
Patent number
US06057369

Reaction notes

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