Ninhydrin → (S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate

HRID 1616058Notes

Reaction equation

HRID 1616058 reaction equation
[C:1]([NH:8][C@H:9]([C:11]([OH:13])=O)[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH3:27][NH:28][O:29][CH3:30].C1C=C2C(C(O)(O)C(=O)C2=CC=1)=O>C(Cl)Cl>[CH3:30][O:29][N:28]([CH3:27])[C:11](=[O:13])[C@@H:9]([NH:8][C:1](=[O:2])[O:3][C:4]([CH3:5])([CH3:6])[CH3:7])[CH3:10]

Participants

6

Reactant 4

HCID 10236NinhydrinHCID 682631,1'-CarbonyldiimidazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 85082Tert-butoxycarbonylalanine

Product 1

HCID 11806530(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-Boc-L-alanine (1.0 Kg, 5.29 mol, 1.0 equiv), in DCM (15 L) was added carbonyldiimidazole (943 g, 5.81 mol, 1.1 equiv) and the resultant mixture was stirred for 1 h at rt. To this reaction mixture was added N,O-dimethylhydroxylamine hydrochloride (577 g, 5.92 mol, 1.12 equiv) and stirred at rt for 16 h. The reaction was monitored using TLC (Note: for TLC, ninhydrin stain was used to visualize the product). Another 800 g batch was combined with this batch prior to the work up. Upon completion DCM was evaporated in vacuo. The crude residue thus obtained was partitioned between EtOAc (30 L) and water (10 L). The organic layer was then washed with 1 N HCl (2×10.0 L), aq satd. NaHCO3 (2×15.0 L), brine (5 L), and dried over Na2SO4. The aq layer was back extracted with EtOAc (3×15.0 L) and the work up procedure was repeated. Evaporation of solvent in vacuo afforded (S)-tert-butyl 1-(methoxy(methyl)amino)-1-oxopropan-2-ylcarbamate as a white solid.

Workup

  1. customUpon completion DCM was evaporated in vacuo
  2. customThe crude residue thus obtained
  3. customwas partitioned between EtOAc (30 L) and water (10 L)
  4. washThe organic layer was then washed with 1 N HCl (2×10.0 L)
  5. dry with materialNaHCO3 (2×15.0 L), brine (5 L), and dried over Na2SO4
  6. extractionThe aq layer was back extracted with EtOAc (3×15.0 L)
  7. customEvaporation of solvent in vacuo

Sources & evidence

ORD record
ord-ba19226a903e4020a32357c35b86f39d
Source dataset
uspto-grants-2014_07
Patent number
US08765768B2

Reaction notes

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