Triphenylphosphine → (1S)-3-[5-(1-Amino-2-biphenyl-4-yl-ethyl)-tetrazol-1-yl]-propionitrile

HRID 333354Notes

Reaction equation

HRID 333354 reaction equation
[C:1]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]([NH:16]C(=O)OC(C)(C)C)[C:9]([NH:11][CH2:12][CH2:13][C:14]#[N:15])=O)=[CH:3][CH:2]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[Si]([N:67]=[N+:68]=[N-:69])(C)(C)C>C1COCC1>[NH2:16][C@H:8]([C:9]1[N:11]([CH2:12][CH2:13][C:14]#[N:15])[N:69]=[N:68][N:67]=1)[CH2:7][C:4]1[CH:5]=[CH:6][C:1]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:2][CH:3]=1

Participants

6

Reactant 4

HCID 11776Triphenylphosphine3×HCID 78378Azidotrimethylsilane3×HCID 5363146Diisopropyl azodicarboxylate3×HCID 53856625(S)-2-t-butoxycarbonylamino-3-biphenyl-4-yl-N-(2-cyanoethyl)-propionamide

Product 1

HCID 22849544(1S)-3-[5-(1-Amino-2-biphenyl-4-yl-ethyl)-tetrazol-1-yl]-propionitrileYield 73.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-tert-butyl 3-(biphenyl-4-yl)-1-(2-cyanoethylamino)-1-oxopropan-2-ylcarbamate (563 mg, 1.431 mmol) and triphenylphosphine (450 mg, 1.717 mmol) in THF (10 mL) were added DIAD (0.334 mL, 1.717 mmol) and TMSN3 (0.228 mL, 1.717 mmol) at room temperature. After 2 hours, additional triphenylphosphine (180 mg, 0.687 mmol), DIAD (0.134 mL, 0.687 mmol) and TMSN3 (0.0912 mL, 0.687 mmol) were added. After being stirred overnight, additional triphenylphosphine (180 mg, 0.687 mmol), DIAD (0.134 mL, 0.687 mmol) and TMSN3 (0.0912 mL, 0.687 mmol) were added. After being additional 3 hours, the reaction mixture was concentrated and purified by silica gel flash column chromatography (eluent; EtOAc/heptane). The obtained product was treated with 4M HCl in dioxane (10 mL) at room temperature. After being stirred for 1 hour, the reaction mixture was concentrated. The residue was diluted with EtOAc, washed with saturated NaHCO3aq and brine. The organic layer was dried over Na2SO4, concentrated and purified by silica gel flash column chromatography (eluent; MeOH/DCM) to give (S)-3-(5-(1-amino-2-(biphenyl-4-yl)ethyl)-1H-tetrazol-1-yl)propanenitrile (334 mg). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.83 (dt, J=6.82, 16.9 Hz, 1H), 2.96 (dt, J=6.82, 13.89 Hz, 1H), 3.21 (dd, J=8.08, 13.64 Hz, 1H), 3.42 (dd, J=6.06, 13.64 Hz, 1H), 4.47-4.59 (m, 2H), 4.60-4.68 (m, 1H), 7.21 (d, J=8.08 Hz, 2H), 7.33-7.39 (m, 1H), 7.42-7.48 (bt, 2H), 7.54-7.60 (m, 3H).

Workup

  1. waitAfter being additional 3 hours
  2. concentrationthe reaction mixture was concentrated
  3. custompurified by silica gel flash column chromatography (eluent; EtOAc/heptane)
  4. additionThe obtained product was treated with 4M HCl in dioxane (10 mL) at room temperature
  5. stirringAfter being stirred for 1 hour
  6. concentrationthe reaction mixture was concentrated
  7. additionThe residue was diluted with EtOAc
  8. washwashed with saturated NaHCO3aq and brine
  9. dry with materialThe organic layer was dried over Na2SO4
  10. concentrationconcentrated
  11. custompurified by silica gel flash column chromatography (eluent; MeOH/DCM)

Sources & evidence

ORD record
ord-4e981db7539c42d28c534a922b6afafc
Source dataset
uspto-grants-2014_11
Patent number
US08877815B2

Reaction notes

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