Formaldehyde → N-Methylleucine

HRID 1089821Notes

Reaction equation

HRID 1089821 reaction equation
C1C2C(CO[C:16]([NH:18][C@H:19]([C:24]([OH:26])=[O:25])[CH2:20][CH:21]([CH3:23])[CH3:22])=O)C3C(=CC=CC=3)C=2C=CC=1.C=O.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH3:16][NH:18][C@H:19]([C:24]([OH:26])=[O:25])[CH2:20][CH:21]([CH3:23])[CH3:22]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 1549133Fmoc-leucine

Product 1

HCID 2777993N-MethylleucineYield 117.1%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 1140TolueneSolvent

Procedure

A suspension of N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-leucine (1.67 g, 5 mmol) in toluene(100 ml) was charged with paraformaldehyde (1 g, 33.3 mmol) and 4-toluenesulfonic acid (100 mg, catalytic). The mixture was refluxed for 30 minutes in a Dean Stark apparatus for azeotropic distillation. The solution was washed with a saturated solution of sodium bicarbonate (×2), dried over magnesium sulfate and evaporated. The resulting oil in a 1:1 mixture of chloroform:trifluoroacetic acid (50 ml), at room temperature, was charged with triethylsilane (2.38 ml, 15 mmol). Stirring was continued for 22 hr. The solvents were removed in vacuum and the oil was crystallized from a mixture of ether:hexane. Recrystalyzation from EtOAc:hexane afforded 0.85 g (46%) of the product as a colorless solid, mp 101°-3° C.

Workup

  1. temperatureThe mixture was refluxed for 30 minutes in a Dean Stark apparatus for azeotropic distillation
  2. washThe solution was washed with a saturated solution of sodium bicarbonate (×2)
  3. dry with materialdried over magnesium sulfate
  4. customevaporated
  5. additionThe resulting oil in a 1:1 mixture of chloroform
  6. customThe solvents were removed in vacuum
  7. customthe oil was crystallized from a mixture of ether

Sources & evidence

ORD record
ord-53ad8a2361374f15a4ed27622a2ceb26
Source dataset
uspto-grants-1992_01
Patent number
US05079260

Reaction notes

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