Hydrochloric Acid → HCID 67337559, compound

HRID 1671627Notes

Reaction equation

HRID 1671627 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[C@H:12]([C:13]([OH:15])=O)[CH2:11][C@@H:10]([NH:16][C:17]([O:19][CH2:20][CH:21]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]3[C:22]2=[CH:23][CH:24]=[CH:25][CH:26]=3)=[O:18])[CH2:9]1)=[O:7])([CH3:4])[CH3:3].C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.CCN(CC)CC.[F:56][C:57]1[CH:58]=[C:59]([Mg]Br)[CH:60]=[CH:61][CH:62]=1.P([O-])([O-])([O-])=O.Cl>C(Cl)Cl.CCOC(C)=O>[CH:27]1[C:22]2[CH:21]([CH2:20][O:19][C:17]([NH:16][C@H:10]3[CH2:9][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[C@H:12]([C:13](=[O:15])[C:61]4[CH:60]=[CH:59][CH:58]=[C:57]([F:56])[CH:62]=4)[CH2:11]3)=[O:18])[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:23]=2[CH:24]=[CH:25][CH:26]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 1061PhosphateHCID 8471TriethylamineHCID 73910Diphenylphosphinic chlorideHCID 2756135176486-63-8HCID 178505773HCID 178505773, compound

Product 1

HCID 67337559HCID 67337559, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

N-Boc-trans-4-N-Fmoc-amino-L-proline (0.24 g, 0.19 mL, 0.001 mol) in CH2Cl2 (10 mL) was treated with diphenylphosphinic chloride (0.001 mol) at 0° C. in the presence of Et3N (0.10 g, 0.14 mL, 0.001 mol) for 2 h. EtOAc (10 mL) was then added to the mixture, which was then washed successively with H2O (5 mL), saturated NaHCO3 aqueous solution (5 mL), and brine (5 mL), and dried over Na2SO4. The organic layer was concentrated in vacuo, and the resulting residue was dissolved in THF (10 mL). The solution was then cooled to −78° C. 3-Fluorophenylmagnesium bromide solution (1.0 M in THF, 1 mL, 0.001 mol) was added, and the mixture was gradually warmed to room temperature before being poured into a mixture of 0.1 M phosphate buffer (pH=7.2, 5 mL) and 1 M HCl aqueous solution (5 mL) at 0° C. The aqueous layer was extracted with CH2Cl2 (10 mL×3). The combined organic layers were washed successively with saturated aqueous NaHCO3 (10 mL) and brine (10 mL) and dried over Na2SO4. The solvent was evaporated in vacuo, and the residue was purified by column chromatography (silica gel, hexanes:EtOAc=7:3) to afford a white solid (XIII-5, 0.27 g, 50%).

Workup

  1. washwas then washed successively with H2O (5 mL), saturated NaHCO3 aqueous solution (5 mL), and brine (5 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationThe organic layer was concentrated in vacuo
  4. dissolutionthe resulting residue was dissolved in THF (10 mL)
  5. temperaturethe mixture was gradually warmed to room temperature
  6. extractionThe aqueous layer was extracted with CH2Cl2 (10 mL×3)
  7. washThe combined organic layers were washed successively with saturated aqueous NaHCO3 (10 mL) and brine (10 mL)
  8. dry with materialdried over Na2SO4
  9. customThe solvent was evaporated in vacuo
  10. customthe residue was purified by column chromatography (silica gel, hexanes:EtOAc=7:3)
  11. customto afford a white solid (XIII-5, 0.27 g, 50%)

Sources & evidence

ORD record
ord-d6a7d999d5a74acd9ddc0cd73cda28ed
Source dataset
uspto-grants-2011_08
Patent number
US07994326B2

Reaction notes

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