9-Fluorenylmethyl chloroformate → N-Fmoc-hydroxylamine

HRID 879031Notes

Reaction equation

HRID 879031 reaction equation
Cl.[NH2:2][OH:3].[C:4](Cl)([O:6][CH2:7][CH:8]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]2[C:9]1=[CH:10][CH:11]=[CH:12][CH:13]=2)=[O:5]>C(Cl)Cl.O>[OH:3][NH:2][C:4](=[O:5])[O:6][CH2:7][CH:8]1[C:20]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:14]2[C:9]1=[CH:10][CH:11]=[CH:12][CH:13]=2

Participants

5

Reactant 2

HCID 343679-Fluorenylmethyl chloroformateHCID 443297Hydroxyamine hydrochloride

Product 1

HCID 5062222N-Fmoc-hydroxylamineYield 72.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
20 °C

Procedure

hydroxylamine hydrochloride (6.0 g, 86 mmol) in CH2Cl2 (250 mL) and water (100 mL) at 0° C. After 10 mins, solid FmocCl (21 g, 81 mmol) is added portionwise with vigorous stirring. After 1 h a white precipitate forms and more CH2Cl2 (100 mL) is added. The solution is allowed to warm to 20° C. and left to stir for 3 d. The white solid that remains is filtered away, re-dissolved in ethyl acetate (300 mL), washed with brine and dried over MgSO4 to yield (9H-fluoren-9-yl)methyl hydroxycarbamate (Mellor, S. L.; McGuire, C.; Chan, W. C.; Tet. Lett., 1997, 38, 3311-3314) as a white solid (15 g, 68%). Furthermore, the mother-liquor is concentrated and purified by column chromatography (silica gel, ethyl acetate/CH2Cl2 1:1 to 1:0) to yield the title compound (by-product) as a white solid (0.55 g, 1%).

Workup

  1. customat 0° C
  2. waitleft
  3. filtrationThe white solid that remains is filtered away
  4. dissolutionre-dissolved in ethyl acetate (300 mL)
  5. washwashed with brine
  6. dry with materialdried over MgSO4

Sources & evidence

ORD record
ord-6cca889ba34e4be9aea951c474b2abcc
Source dataset
uspto-grants-2015_03
Patent number
US08987504B2

Reaction notes

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