Triphenylphosphine → (2R,4S)-5-Biphenyl-4-yl-4-{3-[1-(2-cyano-ethyl)-1H-tetrazol-5-yl]-propionylamino}-2-methyl-pentanoic acid ethyl ester

HRID 2384082Notes

Reaction equation

HRID 2384082 reaction equation
[CH2:1]([O:3][C:4](=[O:34])[C@H:5]([CH3:33])[CH2:6][C@H:7]([NH:21][C:22](=[O:32])[CH2:23][CH2:24][C:25](=O)[NH:26][CH2:27][CH2:28][C:29]#[N:30])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[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:72]=[N+:73]=[N-:74])(C)C>C1COCC1>[CH2:1]([O:3][C:4](=[O:34])[C@H:5]([CH3:33])[CH2:6][C@H:7]([NH:21][C:22](=[O:32])[CH2:23][CH2:24][C:25]1[N:26]([CH2:27][CH2:28][C:29]#[N:30])[N:74]=[N:73][N:72]=1)[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[CH3:2]

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 75555Diisopropyl diazene-1,2-dicarboxylate2×HCID 78378Azidotrimethylsilane2×HCID 59608195(2R,4S)-5-biphenyl-4-yl-4-[3-(2-cyano-ethylcarbamoyl)-propionylamino]-2-methyl pentanoic acid ethyl ester

Product 1

HCID 59608222(2R,4S)-5-Biphenyl-4-yl-4-{3-[1-(2-cyano-ethyl)-1H-tetrazol-5-yl]-propionylamino}-2-methyl-pentanoic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2R,4S)-5-biphenyl-4-yl-4-[3-(2-cyano-ethylcarbamoyl)-propionylamino]-2-methyl pentanoic acid ethyl ester (150 mg, 0.324 mmol) in THF (2 mL) is added triphenylphosphine (85 mg, 0.324 mmol). After stirring for 10 minutes, diisopropyl azodicarboxylate (0.063 mL, 0.324 mmol) and trimethylsilyl azide (0.043 mL, 0.324 mmol) are added. The mixture is stirred for 8 hours and additional triphenylphosphine, diisopropyl azocarboxylate, and trimethylsilyl azide (each 0.324 mmol) are added. After stirring overnight, the mixture is concentrated and purified by silica gel column chromatography to give (2R,4S)-5-biphenyl-4-yl-4-{3-[1-(2-cyano-ethyl)-1H-tetrazol-5-yl]-propionylamino}-2-methyl-pentanoic acid ethyl ester. HPLC Retention time 1.42 minutes (condition B); MS 489 (M+1); 1H NMR (400 MHz, CDCl3) δ ppm 1.11 (d, J=7.07 Hz, 3H), 1.23 (t, J=7.07 Hz, 3H), 1.47 (ddd, J=4.29, 10.10, 14.39 Hz, 1H), 1.91 (ddd, J=4.04, 9.60, 13.64 Hz, 1H), 2.31-2.41 (m, 1H), 2.67-2.81 (m, 4H), 3.00 (t, J=6.82 Hz, 2H), 3.05-3.17 (m, 2H), 4.03-4.22 (m, 3H), 4.50-4.68 (m, 2H), 5.69 (d, J=9.09 Hz, 1H), 7.14 (d, J=8.08 Hz, 2H), 7.34 (t, J=7.33 Hz, 1H), 7.44 (t, J=7.83 Hz, 2H), 7.50 (d, J=8.34 Hz, 2H), 7.59 (d, J=7.07 Hz, 2H).

Workup

  1. stirringThe mixture is stirred for 8 hours
  2. stirringAfter stirring overnight
  3. concentrationthe mixture is concentrated
  4. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-3e4bff6c2ed24ac98aa2d4fb5f9f3649
Source dataset
uspto-grants-2012_09
Patent number
US08263629B2

Reaction notes

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