Reaction #417907

Reaction equation

Boc-Hfe-OH

(trimethylsilyl)diazomethane

H2NOH.HCl

KOH

HCl

→

solid

Yield 49.9%

N-(1-(N-hydroxycarbamoyl)(1S)-3-phenylpropyl)(tert-butoxy)-carboxamide

Yield 49.9%

Solvents

CH2Cl2 MeOH

MeOH

Et2O

Conditions

Workup

1. 1
   OtherExcess (trimethylsilyl)diazomethane was consumed by the dropwise addition of glacial AcOH
2. 2
   Otherall volatiles removed in vacuo
3. 3
   workup.DISSOLUTIONThe crude ester was redissolved in MeOH (50.0 mL)
4. 4
   workup.WAITAfter 14 h
5. 5
   Otherall volatiles removed in vacuo
6. 6
   OtherThe solids were triturated with several portions of hot EtOAc (5×10 mL)
7. 7
   Otherremoved by filtration through a scintered glass funnel of medium porosity
8. 8
   OtherThe combined filtrates were collected
9. 9
   Concentrationconcentrated in vacuo to an off-white powder
10. 10
    OtherPurification
11. 11
    Otherthrough recrystallization from hot EtOAc (200 mL)

Procedure

A solution of crude Boc-Hfe-OH (10.0 mmol theoretical) in 4:1 CH2Cl2/MeOH (50.0 mL) was treated with (trimethylsilyl)diazomethane (12.0 mmol; 6.00 mL of a 2.0 M solution in Et2O) dropwise over 0.25 h at 22° C. CAUTION: vigorous gas evolution. The resulting yellow solution was stirred an additional 0.25 h to ensure complete methylation. Excess (trimethylsilyl)diazomethane was consumed by the dropwise addition of glacial AcOH, then all volatiles removed in vacuo. The crude ester was redissolved in MeOH (50.0 mL), cooled to 0° C. and treated with a previously prepared suspension of H2NOH.HCl (2.08 g, 30.0 mmol) and KOH (3.37 g, 60.0 mmol) in MeOH (50.0 mL); a large bore cannula needle was required for the transfer. The resulting suspension then warmed slowly to 22° C. overnight as the ice bath melted. After 14 h, the suspension was acidified with conc. HCl to pH 4-5 then all volatiles removed in vacuo. The solids were triturated with several portions of hot EtOAc (5×10 mL) and removed by filtration through a scintered glass funnel of medium porosity. The combined filtrates were collected and concentrated in vacuo to an off-white powder. Purification through recrystallization from hot EtOAc (200 mL) afforded a white microcrystalline solid (1.47 g, 4.99 mmol, 49.9%). The spectral data obtained for this material are in accord with that described for the product of Part 1A.

Source