Oxalyl chloride → (+)-(2R,3S)-3-(3,4-dimethoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid hydroxyamide

HRID 1107153Notes

Reaction equation

HRID 1107153 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 57142747(2R,3S)-3-(3,4-dimethoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid

Product 1

HCID 57151533(+)-(2R,3S)-3-(3,4-dimethoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid hydroxyamideYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

(2R,3S)-3-(3,4-Dimethoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid (0.46 g, 1.2 mmol) is dissolved in CH2Cl2 (4.5 mL) and cooled to 0° C. and to this is added 2 M oxalyl chloride in CH2Cl2 (1.9 mL, 3.8 mmol) over 5 minutes. The ice bath is removed and the reaction allowed to warm to room temperature. After 1.5 hours, the reaction is concentrated in vacuo and azeotroped with chloroform several times. The crude residue is dissolved in CH2Cl2 (4 mL) and O-trimethylsilylhydroxylamine (0.4 g, 3.6 mmol) is added slowly. After 5 minutes, the reaction is diluted with CH2Cl2 (20 mL) and washed with 2 N HCl (15 mL). The aqueous layer is back-extracted with CH2Cl2 (10 mL) and the combined organic layers are washed with water (50 mL), dried over MgSO4 and concentrated in vacuo. The crude residue is azeotroped with ether/petroleum ether and triturated with a large volume of petroleum ether to give (+)-(2R,3S)-3-(3,4-dimethoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid hydroxyamide (0.45 g, 94%): [a]D23 +22° (c=1.0, CHCl3); 1H NMR (300 MHz, CD3OD) δ 7.25-7.21 (m, 2H), 7.15-7.10 (m, 3H), 7.05-6.98 (m, 2H), 6.87 (d, J=8.2 Hz, 1H), 3.81 (s, 3H), 3.80 (s, 3H), 3.17-3.14 (m,1H), 2.58-2.52 (m, 2H), 2.35-2.30 (m, 1H), 1.75-1.65 (m, 1H), 1.60-1.40 (m, 5H), 1.17 (d, J=7.0 Hz, 3H); MS (ion spray) m/e 404 (M+H)+ ; Anal. (C22H29NO4S) C, H, N.

Workup

  1. customThe ice bath is removed
  2. temperatureto warm to room temperature
  3. concentrationthe reaction is concentrated in vacuo
  4. customazeotroped with chloroform several times
  5. dissolutionThe crude residue is dissolved in CH2Cl2 (4 mL)
  6. waitAfter 5 minutes
  7. washwashed with 2 N HCl (15 mL)
  8. extractionThe aqueous layer is back-extracted with CH2Cl2 (10 mL)
  9. washthe combined organic layers are washed with water (50 mL)
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated in vacuo
  12. customThe crude residue is azeotroped with ether/petroleum ether
  13. customtriturated with a large volume of petroleum ether

Sources & evidence

ORD record
ord-43a3eed71e2e435d9eabe0fb81aa5d77
Source dataset
uspto-grants-2000_05
Patent number
US06057369

Reaction notes

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