HCID 87263023, compound → HCID 67086784, compound

HRID 2281571Notes

Reaction equation

HRID 2281571 reaction equation
CC1(C)[O:6][C@H:5]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17][CH:18]([NH:27]S(C(C)(C)C)=O)/[CH:19]=[N:20]/S(C(C)(C)C)=O)=[CH:11][CH:10]=2)[CH2:4][O:3]1.[CH2:35]([Mg]Cl)[CH2:36][CH3:37].C([Mg])CC>C1COCC1.C(OCC)C>[NH2:27][CH:18]([CH:19]([NH2:20])[CH2:35][CH2:36][CH3:37])[CH2:17][CH2:16][CH2:15][C:12]1[CH:11]=[CH:10][C:9]([O:8][CH2:7][C@@H:5]([OH:6])[CH2:4][OH:3])=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 87263023HCID 87263023, compoundHCID 178455848HCID 178455848, compoundHCID 178455855HCID 178455855, compound

Product 1

HCID 67086784HCID 67086784, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-methyl-propane-2-sulfinic acid (4-[4-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenyl]-1-{[(E)-2-methyl-propane-2-sulfinylimino]-methyl}-butyl)-amide (907 mg, 1.7 mmol) in THF (20 ml) at 0° C. n-propylmagnesium chloride (1.76 ml of a 2M solution in diethyl ether, 3.52 mmol). The solution is stirred at 0° C. for 30 minutes then at room temperature for 3 hours. A further portion of n-propylmagnesium (1.76 ml of a 2M solution in diethyl ether, 3.52 mmol) is added and the mixture is stirred at room temperature overnight. The resulting mixture is quenched with sat. aq. NH4Cl solution (50 ml) and extracted with EtOAc (2×50 ml). The organic phase is dried (MgSO4) and concentrated in vacuo. The residue is dissolved in EtOAc (10 ml) and treated with 4M HCl/dioxan (10 ml). After 10 minutes, the solution is concentrated in vacuo and the residue diluted with DCM (100 ml). This is treated with sat. aq. NaHCO3 solution (100 ml) and the organic phase is removed and dried (MgSO4). The DCM solution is applied to a SCX-2 cartridge (10 g) and this is eluted with DCM and MeOH. The product is released with 2M NH3 in MeOH, and the methanolic ammonia fraction concentrated to give (S)-3-[4-(4,5-Diamino-octyl)-phenoxy]-propane-1,2-diol as a mixture of diastereomers as a gum; [M+H]+ 515.38

Workup

  1. customat 0° C.
  2. waitat room temperature for 3 hours
  3. stirringthe mixture is stirred at room temperature overnight
  4. customThe resulting mixture is quenched with sat. aq. NH4Cl solution (50 ml)
  5. extractionextracted with EtOAc (2×50 ml)
  6. dry with materialThe organic phase is dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue is dissolved in EtOAc (10 ml)
  9. additiontreated with 4M HCl/dioxan (10 ml)
  10. waitAfter 10 minutes
  11. concentrationthe solution is concentrated in vacuo
  12. additionthe residue diluted with DCM (100 ml)
  13. additionThis is treated with sat. aq. NaHCO3 solution (100 ml)
  14. customthe organic phase is removed
  15. dry with materialdried (MgSO4)
  16. washthis is eluted with DCM and MeOH
  17. concentrationthe methanolic ammonia fraction concentrated

Sources & evidence

ORD record
ord-8295d3e9001a4f2dbcd14a32ec8bce20
Source dataset
uspto-grants-2015_09
Patent number
US09139586B2

Reaction notes

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