(2S)-[[N-(tert-Butoxycarbonyl)-N-methyl-L-alanyl]amino](cyclohexyl)ethanoic acid → tert-Butyl methylcarbamate

HRID 1034608Notes

Reaction equation

N1CCC[C@H]1C1C=C(C=O)C=NC=1.[C:14]([O:18][C:19]([N:21](C)[C@@H:22](C)C(N[C@@H](C1CCCCC1)C(O)=O)=O)=[O:20])([CH3:17])([CH3:16])[CH3:15].O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>C1COCC1.CCOC(C)=O>[C:14]([O:18][C:19](=[O:20])[NH:21][CH3:22])([CH3:17])([CH3:16])[CH3:15]

Participants

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)-ethyl]-methyl-carbamic acid tert-butyl ester (6) (5.0 g, yield 88%) as pale yellow solid.

Workup

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

Sources & evidence

ORD record: ord-01f4db2b68a444eda1b38aff5c57116e
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546336B2

Reaction notes

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