4-Methylmorpholine → Tert-butoxycarbonylamino-[4-(diethoxy-phosphoryl)-phenyl]-acetic acid benzyl ester

HRID 32810

Reaction equation

HRID 32810 reaction equation
[CH2:1]([O:8][C:9](=[O:33])[CH:10]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:11]1[CH:16]=[CH:15][C:14](OS(C(F)(F)F)(=O)=O)=[CH:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:34]([O:36][P:37]([O-:41])[O:38][CH2:39][CH3:40])[CH3:35].CN1CCOCC1>C(#N)C.C(OCC)(=O)C>[CH2:1]([O:8][C:9](=[O:33])[CH:10]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:30])[CH3:31])=[O:27])[C:11]1[CH:12]=[CH:13][C:14]([P:37]([O:38][CH2:39][CH3:40])([O:36][CH2:34][CH3:35])=[O:41])=[CH:15][CH:16]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 79724-MethylmorpholineHCID 3780918DiethylphosphiteHCID 17999119(S)-Benzyl 2-(tert-butoxycarbonylamino)-2-(4-(trifluoromethylsulfonyloxy)phenyl)acetate

Product 1

HCID 86603382Tert-butoxycarbonylamino-[4-(diethoxy-phosphoryl)-phenyl]-acetic acid benzyl esterYield 93.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
75 °C

Procedure

To a solution of tert-butoxycarbonylamino-(4-trifluoromethane-sulfonyloxy-phenyl)-acetic acid benzyl ester (2.2 g, 4.50 mmol) in acetonitrile (10 mL) was added diethylphosphite (643 μL, 5.00 mmol) followed by N-methylmorpholine (691 μL, 6.30 mmol). The mixture was purged with nitrogen and tetrakis-triphenylphosphine palladium (260 mg, 0.23 mmol, 15 mol %) was added. The reaction mixture was heated to 75° C. overnight then cooled to room temperature and diluted with ethyl acetate (50 mL). The mixture was poured into a separatory funnel containing ethyl acetate (100 mL) and washed with 0.2M aqueous hydrochloric acid (2×), water (2×), brine and dried over sodium sulfate. The solvent was removed in vacuo, and the product was chromatographed over silica gel gradient eluted between 10 to 75% ethyl acetate in hexanes to afforded tert-butoxycarbonylamino-[4-(diethoxy-phosphoryl)-phenyl]-acetic acid benzyl ester (2.0 g, 93%).

Workup

  1. additionwas added
  2. temperaturethen cooled to room temperature
  3. additionThe mixture was poured into a separatory funnel
  4. washwashed with 0.2M aqueous hydrochloric acid (2×), water (2×), brine
  5. dry with materialdried over sodium sulfate
  6. customThe solvent was removed in vacuo
  7. customthe product was chromatographed over silica gel gradient
  8. washeluted between 10 to 75% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-b083c6ce8eba4d4884b0bfed0a1c56ed
Source dataset
uspto-grants-2008_09
Patent number
US07427635B2

Linked notes

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