Triphenylphosphine → HCID 71086365, compound

HRID 528987Notes

Reaction equation

HRID 528987 reaction equation
[C:1]([O:5][C:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:15]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[N:16][N:17]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:18]=2[CH2:19][CH2:20][CH2:21][CH3:22])=[C:10]([C:34]([N:36]2[C@H:45]([CH2:46]O)[CH2:44][C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH2:37]2)=[O:35])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].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.P([N:97]=[N+:98]=[N-:99])(=O)(OC1C=CC=CC=1)OC1C=CC=CC=1>C1COCC1.CCOC(C)=O>[N:97]([CH2:46][C@@H:45]1[CH2:44][C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH2:37][N:36]1[C:34]([C:10]1[CH:9]=[C:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH:13]=[CH:12][C:11]=1[C:14]1[C:15]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[N:16][N:17]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:18]=1[CH2:19][CH2:20][CH2:21][CH3:22])=[O:35])=[N+:98]=[N-:99]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 123414Diphenylphosphoryl azideHCID 5363146Diisopropyl azodicarboxylateHCID 86718932HCID 86718932, compound

Product 1

HCID 71086365HCID 71086365, compoundYield 73.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of ethyl 4-(4-(tert-butoxycarbonyl)-2-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-butyl-1-phenyl-1H-pyrazole-3-carboxylate (113 mg, 0.177 mmol) in THF (2 mL) was added triphenylphosphine (55.8 mg, 0.213 mmol) followed by DIAD (0.041 mL, 0.213 mmol) and diphenyl phosphorazidate (58 mg, 0.21 mmol). After stirring at room temperature overnight, a second addition of all three reagents was added (1.2 eq each) and stirring was continued for 3 h. The reaction mixture was diluted with EtOAc, washed with sat. aq. sodium bicarbonate, dried over anhydrous sodium sulfate and concentrated in vacuo. The crude material was purified by flash chromatography (Isco 40 g column eluting with 0-50% EtOAc/hexanes) to give the title compound (86 mg, 73%). 1H NMR (CDCl3, 1:1 mixture of amide rotamers) δ 8.25 (s, 0.5H), 8.15-8.10 (m, 1H), 7.97 (s, 0.5H), 7.51-7.34 (m, 5H), 7.25-6.90 (m, 5H), 5.04-4.97 (m, 1.5H), 4.41-3.97 (m, 3.5H), 3.50-3.01 (m, 3.5H), 2.88-2.46 (m, 3.5H), 1.66-1.62 (m, 3H), 1.61 (s, 4.5H), 1.60 (s, 4.5H), 1.18-0.94 (m, 4H), 0.64-0.56 (m, 3H); MS(ESI) m/z 663.5 (M+H)+.

Workup

  1. additiona second addition of all three reagents
  2. additionwas added (1.2 eq each)
  3. stirringstirring
  4. waitwas continued for 3 h
  5. washwashed with sat. aq. sodium bicarbonate
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by flash chromatography (Isco 40 g column eluting with 0-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-91f3427f4b604e64b0829f2711170e5f
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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