Triethylamine → HCID 68662766, compound

HRID 733340Notes

Reaction equation

HRID 733340 reaction equation
[C:1]([O:5][C:6](=[O:31])[NH:7][CH:8]([CH2:22][C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[C:25]([F:30])[CH:24]=1)[CH:9]([OH:21])[CH2:10][NH:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][CH3:20])[CH:14]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH2:39]([O:46][C:47](Cl)=[O:48])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.CCCCCCC.CCOC(C)=O>C1COCC1>[CH2:39]([O:46][C:47](=[O:48])[N:11]([CH2:10][CH:9]([OH:21])[CH:8]([NH:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:31])[CH2:22][C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[C:25]([F:30])[CH:24]=1)[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][CH3:20])[CH:14]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 21899848Ethylacetate heptaneHCID 57487425HCID 57487425, compound

Product 1

HCID 68662766HCID 68662766, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [1-(3,5-difluoro-benzyl)-3-(3-ethyl-benzylamino)-2-hydroxy-propyl]-carbamic acid tert-butyl ester (16.1 g, 37 mmol) and triethylamine (6.2 mL, 44 mmol) in 80 mL of anhydrous THF under N2 at 0° C. is added benzylchloroformate (5.8 mL, 41 mmol). The solution is warmed to ambient temperature and stirred for 16 h. The solution is quenched with brine and concentrated to remove most of the THF. The residue is diluted with ethyl acetate and separated. The organic phase is washed with 1 M KH2PO4, saturated NaHCO3 and dried over Na2SO4. The mixture is filtered and concentrated to a white solid which is purified on a BIOTAGE 40M column eluting with 400 mL of heptane followed by 4/1:heptane/EtOAc to obtain [3-tert-butoxycarbonylamino-4-(3,5-difluoro-phenyl)-2-hydroxy-butyl]-(3-ethyl-benzyl)-carbamic acid benzyl ester as a white solid (15 g, 26 mmol, 71%), (MS:M+H: 569.4). This compound (6.0 g, 11 mmol) is dissolved in 10 mL of anhydrous CH2Cl2 at 0° C. and 10 mL of TFA is added. The solution is warmed to ambient temperature and stirred for 3 h. The solution is concentrated, diluted with EtOAc and washed with 1M NaOH. The combined organics are dried (Na2SO4) and the mixture is filtered and concentrated to give desired compound as a white solid (5.0 g, 11 mmol, quant. yield), (MS:M+H, 469.5).

Workup

  1. customThe solution is quenched with brine
  2. concentrationconcentrated
  3. customto remove most of the THF
  4. additionThe residue is diluted with ethyl acetate
  5. customseparated
  6. washThe organic phase is washed with 1 M KH2PO4, saturated NaHCO3
  7. dry with materialdried over Na2SO4
  8. filtrationThe mixture is filtered
  9. concentrationconcentrated to a white solid which
  10. customis purified on a BIOTAGE 40M column
  11. washeluting with 400 mL of heptane

Sources & evidence

ORD record
ord-0d3f9e7be08f430f865876dd303428dc
Source dataset
uspto-grants-2009_09
Patent number
US07589094B2

Reaction notes

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