Dimethylformamide → HCID 18790138, compound

HRID 1107140Notes

Reaction equation

HRID 1107140 reaction equation
[C:1]1([S:7]([CH2:10][CH2:11][CH:12]([CH:16]([S:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([O:36][CH3:37])[CH:29]=2)[CH2:17][CH2:18][CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:13](O)=[O:14])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(C=O)C.C(Cl)(=O)C(Cl)=O.C[Si](C)(C)[O:51][NH2:52]>C(Cl)Cl>[OH:51][NH:52][C:13](=[O:14])[CH:12]([CH2:11][CH2:10][S:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)(=[O:9])=[O:8])[CH:16]([S:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([O:36][CH3:37])[CH:29]=1)[CH2:17][CH2:18][CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 18790107HCID 18790107, compound

Product 1

HCID 18790138HCID 18790138, compoundYield 189.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution containing (-)-2-(2-benzenesulfonylethyl)-3-(3,4-dimethoxyphenylsulfanyl)-7-phenylheptanoic acid (285 mg, 0.53 mmol) in anhydrous CH2Cl2 (10 mL) under nitrogen atmosphere is added anhydrous DMF (41 μL, 0.53 mmol) followed by oxalyl chloride (2 M in CH2Cl2, 0.66 mL, 1.31 mmol). The yellow solution is stirred for 30 minutes then O-(trimethylsilyl)hydroxylamine (0.32 mL, 2.65 mmol) is added dropwise. The resulting white precipitate is stirred for 10 minutes then partitioned between 1 N HCl (50 mL) and ethyl acetate (50 mL). The aqueous layer is extracted with ethyl acetate (2×20 mL) and the combined organic extracts are washed with water (30 mL), brine (30 mL), dried over anhydrous MgSO4, filtered and concentrated to afford a pale yellow oil. The crude product is combined with the product of a reaction performed on identical scale and chromatographed on silica gel (CH2Cl2 →CH2Cl2 :MeOH, 19:1) to afford (-)-N-hydroxy-2-(2-benzenesulfonylethyl)-3-(3,4-dimethoxyphenylsulfanyl)-7-phenylheptanamide (560 mg, 95%) as a cream-colored foam. TLC analysis [pet-ether/EtOAc, 1:2, Rf (carboxylic acid)=0.45, Rf (hydroxamate)=0.40]. [α]23D -28° (c 1.1, CHCl3); 1H NMR (300 MHz, CDCl3) δ 1.40-1.80 (m, 6H), 2.10 (m, 1H), 2.22 (m, 1H), 2.60 (m, 2H), 2.68 (m, 1H), 3.05 (broad s, 3H), 3.83 (s, 3H), 3.84 (s, 3H), 6.76 (d, J=8.7 Hz, 1H), 6.98 (m, 2H), 7.12 (m, 3H), 7.28 (m, 2H), 7.52 (m, 2H), 7.64 (t, J=7.3 Hz, 1H), 7.84 (d, J=7.4 Hz, 2H), 8.85 (broad s, 1H) ppm. Mass spectrum (FAB) m/z 557 (M)+.

Workup

  1. stirringThe resulting white precipitate is stirred for 10 minutes
  2. customthen partitioned between 1 N HCl (50 mL) and ethyl acetate (50 mL)
  3. extractionThe aqueous layer is extracted with ethyl acetate (2×20 mL)
  4. washthe combined organic extracts are washed with water (30 mL), brine (30 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford a pale yellow oil
  9. customchromatographed on silica gel (CH2Cl2 →CH2Cl2 :MeOH, 19:1)

Sources & evidence

ORD record
ord-b562017a2ae649029033ec6b8d957d9f
Source dataset
uspto-grants-2000_05
Patent number
US06057369

Reaction notes

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