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

HRID 327615Notes

Reaction equation

HRID 327615 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:20][CH:19]=1)[C:10]([NH:12][CH2:13][CH2:14][C:15]#[N:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C[Si]([N:67]=[N+:68]=[N-:69])(C)C.[SiH3]N=[N+]=[N-]>C(#N)C.C(OCC)(=O)C.CCCCCC>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:10]1[N:12]([CH2:13][CH2:14][C:15]#[N:16])[N:69]=[N:68][N:67]=1)[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:20][CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 78378AzidotrimethylsilaneHCID 139627Silyl azideHCID 53856625(S)-2-t-butoxycarbonylamino-3-biphenyl-4-yl-N-(2-cyanoethyl)-propionamide

Product 1

HCID 54083632(S)-3-[5-(1-t-butoxycarbonylamino-2-biphenyl-4-yl-ethyl)tetrazol-1-yl]-propionitrile

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a stirred solution of (S)-2-t-butoxycarbonylamino-3-biphenyl-4-yl-N-(2-cyanoethyl)-propionamide (20 g, 51.2 mmol) in acetonitrile (220 mL) under nitrogen is added triphenyl phosphine (33.6 g, 128 mmol). The suspension is cooled to 0°. Diisopropyl azodicarboxylate (24.8 mL, 125.6 mmol) is placed in an addition funnel. In a separate addition funnel is placed trimethylsilyl azide (16.8 mL, 127.2 mmol). The two reagents are introduced dropwise, allowing the azoester to be added about 1 minute faster than the silyl azide and keeping the reaction temperature below 10°. The slightly yellow suspension is gradually (10°/hour) warmed up to 35°. The reaction is then monitored by TLC (ethyl acetate/hexane:3/1) until practically complete conversion is observed. A clear solution is then usually obtained. The excess of azide is destroyed by cooling the solution to 10° and adding sodium nitrite (3.2 g) in water (16 mL), followed by acetic acid (16 mL). The mixture is stirred at 20°-25° for at least 2 hours, until a nitrite-free aliquot of the acetonitrile layer shows a negative zide test (ferric chloride paper). The lower salt phase is separated and the organic layer is concentrated in vacuo at 45°. The semi-solid residue is dissolved in isopropanol at 80°. Some insoluble material is filtered from the hot solution. The title compound crystallizes at about 60° after seeding. The suspension is cooled to 25° within 2 hours then left at 0°-5° for 1 hour. The product is filtered, washed with cold ispropanol (3×20 mL) and dried under reduced pressure at 50° to constant weight to obtain (S)-3-[5-(1-t-butoxycarbonylamino-2-biphenyl-4-yl-ethyl)-tetrazol-1-yl]-propionitrile.

Workup

  1. temperatureThe suspension is cooled to 0°
  2. additionIn a separate addition funnel
  3. additionThe two reagents are introduced dropwise
  4. customthe reaction temperature below 10°
  5. temperaturewarmed up to 35°
  6. customA clear solution is then usually obtained
  7. customThe excess of azide is destroyed
  8. temperatureby cooling the solution to 10°
  9. additionadding sodium nitrite (3.2 g) in water (16 mL)
  10. customThe lower salt phase is separated
  11. concentrationthe organic layer is concentrated in vacuo at 45°
  12. dissolutionThe semi-solid residue is dissolved in isopropanol at 80°
  13. filtrationSome insoluble material is filtered from the hot solution
  14. customThe title compound crystallizes at about 60° after seeding
  15. temperatureThe suspension is cooled to 25° within 2 hours
  16. filtrationThe product is filtered
  17. washwashed with cold ispropanol (3×20 mL)
  18. customdried under reduced pressure at 50° to constant weight

Sources & evidence

ORD record
ord-c9b4e305865b4c5485bb9b851042738e
Source dataset
uspto-grants-1993_12
Patent number
US05273990

Reaction notes

Loading…