Oxalyl chloride → HCID 76125203, compound

HRID 1107171Notes

Reaction equation

HRID 1107171 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([C@H:12]([CH2:26][CH2:27][CH2:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C@H:13]([CH2:17][CH2:18][O:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14](O)=[O:15])(=[O:11])=[O:10])=[CH:5][CH:4]=1.C(Cl)(=O)C(Cl)=O.C[Si](C)(C)[O:44][NH2:45]>C(Cl)Cl>[OH:44][NH:45][C:14](=[O:15])[CH:13]([CH2:17][CH2:18][O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH:12]([S:9]([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)(=[O:11])=[O:10])[CH2:26][CH2:27][CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 65578Oxalyl chlorideHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 53875398HCID 53875398, compound

Product 1

HCID 76125203HCID 76125203, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

(±)-(2R*,3R*)-3-(4-Methoxybenzenesulfonyl)-7-phenyl-2-(2-phenoxyethyl)heptanoic acid (0.17 g, 0.34 mmol) is dissolved in CH2Cl2 (1 mL) and cooled to 0° C. A solution of oxalyl chloride in CH2Cl2 (0.5 mL, 1 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 (0.16 g, 1.7 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. The product is purified by reverse phase HPLC (65% CH3CN in 0.1% TFA/H2O) to yield (±)-(2R*, R*)-3-(4-methoxybenzenesulfonyl)-7-phenyl-2-(2-phenoxyethyl)heptanoic acid hydroxyamide (0.12 g, 69%): 1H NMR (300 MHz, CDCl3) δ 7.73 (d, J=8.8 Hz, 2H), 7.28-7.14 (m, 5H), 7.08 (d, J=7.0 Hz, 2H), 6.97-6.89 (m, 3H), 6.73 (d, J=8.1 Hz, 2H), 3.89-3.71 (m, 5H), 3.27-3.20 (m, 2H), 2.51 (t, J=7.2 Hz, 2H), 2.45-2.32 (m, 1H), 1.98-1.75 (m, 3H), 1.55-1.38 (m, 3H), 1.35-1.22 (m, 1H); 13C NMR (75.5 MHz, CDCl3) δ 168.74, 164.06, 158.25, 141.93, 130.70, 129.46, 128.88, 128.34, 128.30, 125.78, 121.06, 114.63, 114.36, 66.37, 65.16, 55.67, 38.36, 35.30, 31.00, 30.35, 27.75, 25.34; MS (FAB) m/e 512 (M+H)+ ; Anal. (C28H33NO6S.0.2 H2O) C, H, N.

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
  14. customThe product is purified by reverse phase HPLC (65% CH3CN in 0.1% TFA/H2O)

Sources & evidence

ORD record
ord-235d6a5701e340f7a122f136851b70cb
Source dataset
uspto-grants-2000_05
Patent number
US06057369

Reaction notes

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