Hydrochloric Acid → HCID 69299427, compound

HRID 2218127Notes

Reaction equation

HRID 2218127 reaction equation
[C:1]([CH2:4][CH:5]([C:7]1[CH:17]=[CH:16][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:9][CH:8]=1)[CH3:6])([OH:3])=O.C(Cl)(=O)C(Cl)=O.[C:24]1([C@@H:30]([CH2:32][OH:33])[NH2:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(N(CC)CC)C.Cl>ClCCl.CN(C)C=O>[OH:33][CH2:32][C@@H:30]([NH:31][C:1]([CH2:4][CH:5]([C:7]1[CH:17]=[CH:16][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:9][CH:8]=1)[CH3:6])=[O:3])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 1347972-Amino-2-phenylethan-1-olHCID 69300009HCID 69300009, compound

Product 1

HCID 69299427HCID 69299427, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of ethyl 4-(2-carboxy-1-methylethyl)benzoate (J. I. DeGraw et al. J. Med. Chem. 1986, 29, 1056) (3.54 g, 15 mmol) in dichloromethane (100 mL) cooled in an ice bath was added oxalyl chloride (3.9 mL, 45 mmol). Dimethylformamide (0.1 mL) was added and the mixture stirred at room temperature for 2 hours, then concentrated under reduced pressure. The residual acid chloride was dissolved in dichloromethane (60 mL) and added to an ice-cooled mixture of (S)-2-phenylglycinol (2.72 g, 20 mmol) and triethylamine (6.3 mL, 45 mmol) in dichloromethane (60 mL) over 30 minutes. The reaction mixture was stirred at room temperature for 1 hour. 2N Hydrochloric acid was added, the organic phase was separated, then washed with water, dried (anhydrous magnesium sulfate) and evaporated. The diastereomeric products were separated by flash chromatography with elution by ethyl acetate, then ethyl acetate-methanol (9:1). There were obtained an earlier eluting (SS) diastereomer (P14a); TLC (silica gel; ethyl acetate) Rf 0.36; MS (ES+ve): [M+H]+ at m/z 356 (C21H25NO4 requires [M+H]+ at m/z 356); and a later eluting (RS) diastereomer (P14b); TLC (silica gel; ethyl acetate) Rf 0.19; MS (ES+ve): [M+H]+ at m/z 356 (C21H25NO4 requires [M+H]+ at m/z 356).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residual acid chloride was dissolved in dichloromethane (60 mL)
  3. additionadded to an ice-
  4. temperaturecooled
  5. stirringThe reaction mixture was stirred at room temperature for 1 hour
  6. customthe organic phase was separated
  7. washwashed with water
  8. dry with materialdried (anhydrous magnesium sulfate)
  9. customevaporated
  10. customThe diastereomeric products were separated by flash chromatography with elution by ethyl acetate
  11. customThere were obtained
  12. washan earlier eluting (SS) diastereomer (P14a)
  13. washand a later eluting (RS) diastereomer (P14b)

Sources & evidence

ORD record
ord-9f59e9a48e6044188153e18a40d1bc53
Source dataset
uspto-grants-2008_08
Patent number
US07410984B2

Reaction notes

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