4-Methylmorpholine → tert-butyl (S)-1-((1S*,2R*,4R*)-4-azido-2-(phenylsulfonylmethyl)cyclohexylamino)-4-(methylthio)-1-oxobutan-2-ylcarbamate

HRID 351390

Reaction equation

HRID 351390 reaction equation
FC(F)(F)C(O)=O.[N:8]([C@@H:11]1[CH2:16][CH2:15][C@H:14]([NH2:17])[C@H:13]([CH2:18][S:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)(=[O:21])=[O:20])[CH2:12]1)=[N+:9]=[N-:10].CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.[NH:55]([C:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])[C@H:56]([C:61](O)=[O:62])[CH2:57][CH2:58][S:59][CH3:60].CN1CCOCC1>CN(C=O)C.CCOC(C)=O>[N:8]([C@@H:11]1[CH2:16][CH2:15][C@H:14]([NH:17][C:61](=[O:62])[C@@H:56]([NH:55][C:64](=[O:65])[O:66][C:67]([CH3:68])([CH3:69])[CH3:70])[CH2:57][CH2:58][S:59][CH3:60])[C@H:13]([CH2:18][S:19]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)(=[O:21])=[O:20])[CH2:12]1)=[N+:9]=[N-:10]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 89857Boc-L-methionineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 131726281(1S*,2R*,4R*)-4-azido-2-benzenesulfonylmethyl-cyclohexylamine trifluoroacetate

Product 1

HCID 131726280tert-butyl (S)-1-((1S*,2R*,4R*)-4-azido-2-(phenylsulfonylmethyl)cyclohexylamino)-4-(methylthio)-1-oxobutan-2-ylcarbamateYield 84.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(1S*,2R*,4R*)-4-azido-2-benzenesulfonylmethyl-cyclohexylamine trifluoroacetate (see 37c) (2.5 g, 6.3 mmol) was dissolved in DMF (15 mL) prior to the addition of BOP reagent (3.4 g) and N-Boc-L-Met-OH (1.9 g). After cooling to 0° C., NMM (2.6 mL) was added. The resulting mixture was warmed to rt and was stirred overnight. The solution was diluted with EtOAc, and was washed successively with brine and sat. NaHCO3. The organic phase was dried (MgSO4), filtered, and concentrated. Flash chromatography of the resulting residue gave tert-butyl (S)-1-((1S*,2R*,4R*)-4-azido-2-(phenylsulfonylmethyl)cyclohexylamino)-4-(methylthio)-1-oxobutan-2-ylcarbamate (2.8 g) as a mixture of diastereomers. MS found: (M+H)+=526.2.

Workup

  1. temperatureThe resulting mixture was warmed to rt
  2. washwas washed successively with brine and sat. NaHCO3
  3. dry with materialThe organic phase was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-cd281643e9fb442fbd1861930cebe5bc
Source dataset
uspto-grants-2007_02
Patent number
US07183270B2

Linked notes

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