2,6-Lutidine → HCID 10135702, compound

HRID 1279798Notes

Reaction equation

HRID 1279798 reaction equation
[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([CH2:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22])[N:16]=2)[CH2:11][C:12](O)=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N1C(C)=CC=CC=1C.ClC(OCC(C)C)=O.C[Si](C)(C)[O:45][NH2:46]>ClCCl.CO>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([CH2:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22])[N:16]=2)[CH2:11][C:12]([NH:46][OH:45])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 79372,6-LutidineHCID 62365Isobutyl chloroformateHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 59909801HCID 59909801, compound

Product 1

HCID 10135702HCID 10135702, compoundYield 45.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (3R)-6-cyclohexyl-3-{3-[(propylsulfonyl)methyl]-1,2,4-oxadiazol-5-yl}hexanoic acid (Preparation 97) (298 mg, 0.77 mmol) and 2,6-lutidine (135 μl, 1.16 mmol) in dichloromethane (10 ml) was cooled to 0° C., treated with isobutyl chloroformate (100 μl, 0.77 mmol) and stirred under a nitrogen atmosphere for 1 hour. O-(Trimethylsilyl)hydroxylamine (310 μl, 2.31 mmol) was added and the mixture was stirred for 4 hours, being allowed to warm to room temperature over this time. The mixture was then treated with methanol (5 ml) and stirred at room temperature for 1 hour. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate and washed with hydrochloric acid (1M) and brine, dried over anhydrous magnesium sulphate, filtered and the solvent removed under reduced pressure. The oil was purified by column chromatography on silica gel eluting with a gradient system of 100:0 (dichloromethane:methanol) gradually changing to 95:5 (dichloromethane:methanol) to afford the title compound as a white solid (140 mg).

Workup

  1. stirringthe mixture was stirred for 4 hours
  2. stirringstirred at room temperature for 1 hour
  3. customThe solvent was removed under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with hydrochloric acid (1M) and brine
  6. dry with materialdried over anhydrous magnesium sulphate
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure
  9. customThe oil was purified by column chromatography on silica gel eluting with a gradient system of 100:0 (dichloromethane:methanol)

Sources & evidence

ORD record
ord-6a7de42de06748188e612cb5c7d44d35
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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