Trimethylsilyl triflate → HCID 71225414, compound

HRID 1427786Notes

Reaction equation

HRID 1427786 reaction equation
C[Si](OS(C(F)(F)F)(=O)=O)(C)C.[Cl:13][C:14]([Cl:52])([Cl:51])[CH2:15][O:16][C:17]([C@@H:19]1[CH2:24][CH2:23][CH2:22][N:21]([C:25](=[O:50])[C@@H:26]([NH:42][C:43](OC(C)(C)C)=[O:44])[CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[CH:29]=2)[NH:20]1)=[O:18].C(N(CC)C(C)C)(C)C.[C:62]([O:66][C:67]([NH:69][C@@H:70]([CH2:74][C:75]1[CH:80]=[CH:79][C:78]([O:81][CH3:82])=[CH:77][CH:76]=1)C(O)=O)=[O:68])([CH3:65])([CH3:64])[CH3:63]>ClCCl.C(#N)C>[Cl:13][C:14]([Cl:52])([Cl:51])[CH2:15][O:16][C:17]([C@@H:19]1[CH2:24][CH2:23][CH2:22][N:21]([C:25](=[O:50])[C@@H:26]([NH:42][C:43](=[O:44])[C@@H:70]([NH:69][C:67]([O:66][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:68])[CH2:74][C:75]2[CH:76]=[CH:77][C:78]([O:81][CH3:82])=[CH:79][CH:80]=2)[CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([O:34][Si:35]([C:38]([CH3:39])([CH3:41])[CH3:40])([CH3:37])[CH3:36])[CH:29]=2)[NH:20]1)=[O:18]

Participants

7

Reactant 4

HCID 65367Trimethylsilyl triflateHCID 81531Diisopropylethylamine2×HCID 2762280Boc-O-methyl-L-tyrosineHCID 71225289HCID 71225289, compound

Product 1

HCID 71225414HCID 71225414, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Trimethylsilyltrifluoromethanesulfonate (341 μL, 1.89 mmol) was added dropwise to a solution of the (S)-1-{(S)-2-tert-butoxycarbonylamino-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionyl}-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (670 mg, 1.05 mmol) in dichloromethane (15 mL) at 0° C. under N2 and the reaction was stirred for 85 minutes. To this was added N,N-diisopropylethylamine (730 μL, 4.19 mmol) and the reaction was warmed to room temperature. The volatiles were evaporated to afford a colourless foam which was dissolved in acetonitrile (15 mL). To this solution was added O-benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluoro-phosphate (477 mg, 1.26 mmol), (S)-2-tert-butoxycarbonylamino-3-(4-methoxy-phenyl)-propionic acid (340 mg, 1.15 mmol) and N,N-diisopropylethylamine (730 μL, 4.19 mmol) and the reaction was stirred for 18 h. The volatiles were evaporated and the residue partitioned between pH=7 buffer and ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the volatiles evaporated. The residue was purified by silica chromatography using a gradient of iso-hexanes/ethyl acetate 3:1 to 1:1 to afford the title compound (570 mg, 67%) as a colourless foam. 1H NMR (300 MHz, CDCl3) δ0.18 (s, 6H), 1.00 (s, 9H), 1.43 (s, 9H), 1.45-1.60 (m, 2H) 1.73-1.83 (m, 1H), 1.85-1.95 (m, 1H), 2.30 (br s, 1H), 2.65-3.00 (m, 5H), 3.50 (d, J=11.2 Hz, 1H), 3.80 (s, 3H), 4.24-4.37 (m, 2H), 4.65 (d, J=11.8 Hz, 1H), 4.95 (d, J=11.8 Hz, 1H), 4.96-5.04 (m, 1H), 5.62-5.75 (m, 1H), 6.45 (d, J=8.3 Hz, 1H), 6.64-6.75 (m, 2H), 6.78-6.86 (m, 3H), 7.07-7.16 (m, 3H). LCMS (m/z) 817.3 [M+H], Tr=5.89 min.

Workup

  1. customThe volatiles were evaporated
  2. customto afford a colourless foam which
  3. stirringthe reaction was stirred for 18 h
  4. customThe volatiles were evaporated
  5. customthe residue partitioned between pH=7 buffer
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. customthe volatiles evaporated
  8. customThe residue was purified by silica chromatography

Sources & evidence

ORD record
ord-007c456b6e4b4f288056d8a2583dc042
Source dataset
uspto-grants-2015_01
Patent number
US08933015B2

Reaction notes

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