Reaktion #47142

Reaktionsgleichung

triflate

1,1′-[[(Propane-1,3-diyl)dioxy]bis[(11S,11aS)-10-(2,2,2-trichloroethoxycarbonyl)-11-(tert-butyldimethylsilyloxy)-7-methoxy-2-[[(trifluoromethyl)sulfonyl]oxy]-1,10,11,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one]]

LiCl

tributyl(phenylethynyl)tin

→

17

Ausbeute 92.7%

1,1′-[[(Propane-1,3-diyl)dioxy]bis[(11S,11aS)-10-(2,2,2-trichloroethoxycarbonyl)-11-(tert-butyldimethylsilyloxy)-7-methoxy-2-ethynylphenyl-1,10,11,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one]]

Ausbeute 92.7%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was heated
2. 2
   Temperaturat reflux for 2.5 h when TLC
3. 3
   Sonstigethe complete consumption of the starting material
4. 4
   Sonstigeexcess solvent was removed
5. 5
   workup.DISSOLUTIONthe residue was dissolved in DCM (20 mL)
6. 6
   Waschenby washing with 10% NH4OH (20 mL)
7. 7
   ExtraktionThe aqueous layer was extracted with DCM (3×20 mL)
8. 8
   Waschenwashed with brine (50 mL)
9. 9
   Trocknendried (MgSO4)
10. 10
    FiltrationFiltration and evaporation of solvent
11. 11
    Sonstigeafforded the crude product which
12. 12
    Sonstigewas purified by flash column chromatography (80:20 v/v hexane/EtOAc)

Vorschrift

A catalytic amount of Pd(PPh3)4 was added to a stirred mixture of triflate 13 (193 mg, 0.13 mmol), LiCl (34 mg, 0.80 mmol, 6.0 eq) and tributyl(phenylethynyl)tin (0.14 mL, 157 mg, 0.40 mmol, 3.0 eq) in dry THF (5 mL). The reaction mixture was heated at reflux for 2.5 h when TLC showed the complete consumption of the starting material. After cooling to room temperature, excess solvent was removed and the residue was dissolved in DCM (20 mL), followed by washing with 10% NH4OH (20 mL). The aqueous layer was extracted with DCM (3×20 mL), and the organic extracts were combined, washed with brine (50 mL) and dried (MgSO4). Filtration and evaporation of solvent afforded the crude product which was purified by flash column chromatography (80:20 v/v hexane/EtOAc) to afford 17 as a yellow glass (162 mg, 90%): 1H NMR (400 MHz, CDCl3) δ 7.40-7.37 (m, 4H, H15), 7.26-7.19 (m, 10H, H3, H6, H16 and H17), 6.70 (s, 2H, H9), 5.85 (d, 2H, J=8.8 Hz, H11), 5.15 (d, 2H, J=12.0 Hz, Troc CH2), 4.24-4.19 (m, 2H, OCH2CH2CH2O), 4.12-4.02 (m, 4H, Troc CH2 and OCH2CH2CH2O), 3.86-3.79 (m, 8H, OCH3×2 and H11a), 3.15 (dd, 2H, J=10.8, 16.5 Hz, H1), 2.63 (d, 2H, J=16.5 Hz, H1), 2.37-2.35 (m, 2H, OCH2CH2CH2O), 0.82 (s, 18H, TBS CH3×6), 0.22 and 0.18 (s×2, 12H, TBS CH3×4); 13C NMR (100.6 MHz, CDCl3) δ 163.8 (Cquat), 153.6 (Cquat), 150.8 (Cquat), 149.3 (Cquat), 133.3 (C3), 131.4 (C15), 128.4 (C16 and C17), 127.8 (Cquat), 125.1 (Cquat), 123.0 (Cquat), 114.0 (C6), 110.0 (C9), 104.8 (Cquat), 95.2 (Troc CCl3), 93.7 (Calkyne), 86.9 (C11), 83.6 (Calkyne), 74.8 (Troc CH2), 66.0 (OCH2CH2CH2O), 61.4 (C11a), 56.2 (OCH3), 37.8 (C1), 28.8 (OCH2CH2CH2O), 25.6 (TBS CH3), 17.8 (TBS Cquat); MS (ES), m/z (relative intensity) 1344 (M+., 8), 625 (100).

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