Oxalyl chloride → (+/-)-3-(4-Methoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid hydroxyamide

HRID 1107185Notes

Reaction equation

HRID 1107185 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9][CH:10]([CH2:16][CH2:17][CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:11]([CH3:15])[C:12](O)=[O:13])=[CH:5][CH:4]=1.C(Cl)(=O)C(Cl)=O.C[Si](C)(C)[O:34][NH2:35]>C(Cl)Cl>[OH:34][NH:35][C:12](=[O:13])[CH:11]([CH3:15])[CH:10]([S:9][C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[CH2:16][CH2:17][CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 65578Oxalyl chlorideHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 18790075(+/-)-3-(4-Methoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid

Product 1

HCID 17915535(+/-)-3-(4-Methoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid hydroxyamideYield 90.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

(±)-3-(4-Methoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid (0.38 g, 1.1 mmol) is dissolved in CH2Cl2 (1 mL) and cooled to 0° C. A solution of oxalyl chloride in CH2Cl2 (0.7 mL, 1.4 mmol) is added dropwise, the bath removed and the reaction allowed to warm and stir at 23° C. for 3 hours. The reaction is then concentrated in vacuo and azeotroped with CHCl3. The resulting oil is dissolved in CH2Cl2 (3 mL), cooled to 0° C. and O-(trimethylsilyl)hydroxylamine (0.4 mL, 3.4 mmol) is added dropwise. The bath is removed and the reaction is allowed to warm to 20° C. The reaction is then partitioned between CH2Cl2 (20 mL) and 1 N HCl (10 mL). The organic layer is then separated and washed with water (10 mL), dried (MgSO4) and concentrated in vacuo to yield (±)-3-(4-methoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid hydroxyamide (0.37 g, 90%) which is used without further purification: 1H NMR (300 MHz, CDCl3) δ 7.30-7.18 (m, 4H), 7.14-7.07 (m, 3H), 7.80-7.73 (m, 2H), 3.73 (s, 1.5H), 3.72 (s, 1.5H), 3.12-3.06 (m, 0.5H), 2.97-2.90 (m, 0.5H), 2.53 (m, 2H), 2.32-2.19 (m, 1H), 1.68-1.25 (m, 6H) 1.16 (d, J=7.0 Hz, 1.5H), 1.11 (d, J=7.0 Hz, 1.5H); MS (FAB) m/e 374 (M+H)+.

Workup

  1. customthe bath removed
  2. temperatureto warm
  3. concentrationThe reaction is then concentrated in vacuo
  4. customazeotroped with CHCl3
  5. dissolutionThe resulting oil is dissolved in CH2Cl2 (3 mL)
  6. temperaturecooled to 0° C.
  7. customThe bath is removed
  8. temperatureto warm to 20° C
  9. customThe reaction is then partitioned between CH2Cl2 (20 mL) and 1 N HCl (10 mL)
  10. customThe organic layer is then separated
  11. washwashed with water (10 mL)
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b5941e8ee76e489b8961746522104807
Source dataset
uspto-grants-2000_05
Patent number
US06057369

Reaction notes

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