Ethyl acetate hexane → HCID 86673454, compound

HRID 2362448Notes

Reaction equation

HRID 2362448 reaction equation
[O:1]=[CH:2][C@@H:3]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]#[C:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:5]=1.[C:26]1([Mg]Br)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(OCC)(=O)C.CCCCCC>O1CCCC1.OP(O)=O.O[Mo](O)(=O)=O>[OH:1][C@@H:2]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C@@H:3]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:22])([CH3:24])[CH3:23])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]#[C:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:5]=1

Participants

6

Reactant 3

HCID 21226206Ethyl acetate hexaneHCID 86673455HCID 86673455, compoundHCID 178418255HCID 178418255, compound2×

Product 1

HCID 86673454HCID 86673454, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 21863154Dihydroxy(dioxo)molybdenum;phosphonic acidCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To (S)-tert-butyl 2-oxo-1-(3-(phenylethynyl)phenyl)ethylcarbamate (95 mg, 0.283 mmol) in tetrahydrofuran (5 mL) at −78° C. was added phenylmagnesium bromide (0.198 mL, 0.595 mmol) dropwise. After half of the phenylmagnesium bromide was added the stir bar stopped spinning due to a gum which formed around it. The ice bath was removed allowing the reaction to warm until the stir bar began to stir again. The addition of Grignard reagent was continued and after 1 h, a fine precipitate was evident. TLC (25% ethyl acetate/hexane; UV and phosphomolybdic acid) showed a single major spot just below starting material (Rf=0.45). After 1.5 h total, the reaction was quenched with 1N HCl (10 mL) and extracted into ethyl acetate (3×10 mL). The combined organics were washed with saturated NaHCO3, brine, dried over MgSO4, filtered and concentrated in vacuo to 126 mg amber oil which was loaded with dichloromethane onto a 12 g silica gel column prepacked with 5% ethyl acetate/hexanes. Elution with 5 to 30% ethyl acetate/hexanes over 250 mL provided 62 mg tert-butyl (1S,2S)-2-hydroxy-2-phenyl-1-(3-(phenylethynyl)phenyl)ethylcarbamate as a colorless oil which was used directly in the next step.

Workup

  1. customformed around it
  2. customThe ice bath was removed
  3. customthe reaction
  4. temperatureto warm until the stir bar
  5. waitAfter 1.5 h total
  6. customthe reaction was quenched with 1N HCl (10 mL)
  7. extractionextracted into ethyl acetate (3×10 mL)
  8. washThe combined organics were washed with saturated NaHCO3, brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo to 126 mg amber oil which
  12. washElution with 5 to 30% ethyl acetate/hexanes over 250 mL

Sources & evidence

ORD record
ord-ac4f00856077435692f7dd8dd12dcdec
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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