Hydrochloric Acid → HCID 51356142, compound

HRID 1874643Notes

Reaction equation

HRID 1874643 reaction equation
[NH2:1][C@H:2]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C@@H:14]([CH3:17])[CH2:15][CH3:16])=[CH:8][CH:7]=1)[C@H:3]([OH:5])[CH3:4].Cl.C(N([CH2:24][CH3:25])CC)C>ClCCl>[OH:5][C@H:3]([CH3:4])[C@H:2]([NH:1][C:3](=[O:5])[C@H:2]([C:25]1[CH:24]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH3:6])[C:6]1[CH:7]=[CH:8][C:9]([O:12][CH2:13][C@@H:14]([CH3:17])[CH2:15][CH3:16])=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 67438257HCID 67438257, compound

Product 1

HCID 51356142HCID 51356142, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (S)-(+)-2-phenylpropionic acid (0.067 g, 0.449 mmol) in dichloromethane (5 mL) in an ice-bath was added oxalyl chloride (0.39 mL, 4.49 mmol), then DMF (0.02 mL) under nitrogen. The reaction mixture was stirred for 30 minutes at 0° C. The excessive solvent was removed on ratovapor and dried under high vacuum for 2 hrs to give the corresponding acid chloride. A separate 50 mL round-bottom flask was charged with (1R,2R)-1-amino-1-[4-((S)-2-methyl-butoxy)phenyl]-propan-2-ol.HCl salt (0.37 mmol), dichloromethane (6 mL) and triethylamine (0.3 mL, 1.85 mmol) in an ice cold bath under nitrogen. The acid chloride mentioned above, in dichloromethane (2 mL) was added into the reaction mixture dropwise. The final reaction mixture was stirred for 1.5 hrs at room temperature. The finished reaction was quenched with water. The organic phase was washed with brine (3×10 mL), dried over MgSO4, filtrated, concentrated in vacuum and purified via column chromatography on silica gel with a gradient of 0%→100% of ethyl acetate in hexane to give a white solid (0.013 g, 10% yield). 1H NMR (400 MHz, CDCl3) δ 7.33 (m, 5H), 6.93 (d, J=8.8 Hz, 2H), 6.80 (m, 2H), 6.05 (d, J=8.3 Hz, 1H), 4.82 (dd, J=8.2, 3.7 Hz, 1H), 4.00 (br. s., 1H), 3.74 (m, 3H), 1.96 (d, J=3.0 Hz, 1H), 1.85 (d, J=6.6 Hz, 1H), 1.54 (m, 3H), 1.27 (m, 2H), 1.16 (d, J=6.3 Hz, 3H), 1.02 (m, 3H), 0.96 (t, J=7.5 Hz, 3H); LCMS (ESI) m/e 370.4 [(M+H), calcd. for C23H32NO3 370.5].

Workup

  1. additionwas added into the reaction mixture dropwise
  2. customThe final reaction mixture
  3. customThe finished reaction
  4. customwas quenched with water
  5. washThe organic phase was washed with brine (3×10 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltrated
  8. concentrationconcentrated in vacuum
  9. custompurified via column chromatography on silica gel with a gradient of 0%→100% of ethyl acetate in hexane

Sources & evidence

ORD record
ord-8df4ba55057a414bad0b25a382870685
Source dataset
uspto-grants-2012_11
Patent number
US08304577B2

Reaction notes

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