Formaldehyde → tert-Butyl ethyl(methyl)carbamate

HRID 1038651Notes

Reaction equation

HRID 1038651 reaction equation
C=O.[C:3]([O:7][C:8]([N:10]([CH3:26])[C@@H:11](C)[C:12](N[C@@H](C1CCCCC1)C(O)=O)=O)=[O:9])([CH3:6])([CH3:5])[CH3:4].O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>C1COCC1.CCOC(C)=O>[C:3]([O:7][C:8](=[O:9])[N:10]([CH2:11][CH3:12])[CH3:26])([CH3:6])([CH3:5])[CH3:4]

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 17748007(2S)-[[N-(tert-Butoxycarbonyl)-N-methyl-L-alanyl]amino](cyclohexyl)ethanoic acidHCID 231494114-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate

Product 1

HCID 14271611tert-Butyl ethyl(methyl)carbamateYield 299.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 4-fluoro-phenyl)-(S)-5-pyrrolidin-2-yl-pyridin-3-yl) -methanone (2.57 g, 9.5 mmole) and (S)-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-cyclohexyl-acetic acid (5) (3.58 g, 10.5 mmole) in 75 mL of THF at 0° C., is added 4-(4,6-dimethoxy-[1,3,5]triazin-2-yl)-4-methyl-morpholinium chloride hydrate (2.97 g, 10.7 mmole) in one portion. After stirring at 20° C. for 2 hours, the reaction mixture is diluted with 100 mL of EtOAc, and washed with 3×20 mL of water. After concentration, the crude product is purified by flash column chromatography (CH2Cl2 95%, MeOH 5%) to give (S) -1-(S)-1-cyclohexyl-2-{(S)-2-[5-(4-fluoro-benzoyl)-pyridin-3-yl]-pyrrolidin-1-yl}-2-oxo-ethylcarbamoyl)-ethylmethyl-carbamic acid tert-butyl ester (6) (5.0 g, yield 88%) as pale yellow solid.

Workup

  1. washwashed with 3×20 mL of water
  2. concentrationAfter concentration
  3. customthe crude product is purified by flash column chromatography (CH2Cl2 95%, MeOH 5%)

Sources & evidence

ORD record
ord-595fac32947e4d16b5f96bf9be29c1b5
Source dataset
uspto-grants-2013_10
Patent number
US08552003B2

Reaction notes

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