Reaction #1340594

Reaction equation

HCl

NaH

LiAlH4

Weinreb amide

(S)-tert-butyl 4-(3-(methoxy(methyl)amino)-3-oxo-2-(tritylamino)propyl)benzylcarbamate

Diethyl ((methylsulfonyl)methyl)phosphonate

→

title compound

(S,E)-tert-butyl 4-(4-(methylsulfonyl)-2-(tritylamino)but-3-en-1-yl)benzylcarbamate

Solvents

EtOAc

EtOAc

Et2O

Et2O

THF

Conditions

Workup

1. 1
   Otherthe layers were separated
2. 2
   ExtractionThe organic layer was extracted with 0.1 M aq. HCl and brine
3. 3
   Dryingdried over MgSO4
4. 4
   Concentrationconcentrated under reduced pressure
5. 5
   Temperaturecooled to 0° C. under an argon atmosphere
6. 6
   workup.STIRRINGthe mixture was stirred at 0° C. for 30 minutes
7. 7
   workup.STIRRINGthe mixture was stirred for 2 hours
8. 8
   Temperaturewhile slowly warming it to room temperature
9. 9
   Extractionthe mixture was extracted with mM aq. HCl (2×) and brine
10. 10
    Dryingdried over MgSO4
11. 11
    Concentrationconcentrated under reduced pressure

Procedure

Weinreb amide 16 (0.65 g, 1.12 mmol) was dissolved in Et2O (15 mL), put under an argon atmosphere and cooled to 0° C. LiAlH4 (2 eq., 2.25 mmol, 0.56 mL of a 4 M solution in Et2O) was added slowly and the mixture was stirred at 0° C. for 1 hour after which TLC analysis indicated complete conversion of the starting compound. 0.1 M aq. HCl (15 mL) was slowly added and the layers were separated. The organic layer was extracted with 0.1 M aq. HCl and brine, dried over MgSO4 and concentrated under reduced pressure. Diethyl ((methylsulfonyl)methyl)phosphonate (1.5 eq., 1.68 mmol, 0.39 g) was dissolved in THF (20 mL) and cooled to 0° C. under an argon atmosphere. NaH (1.5 eq., 1.68 mmol, 67.2 mg, 60% w/w in mineral oil) was slowly added and the mixture was stirred at 0° C. for 30 minutes. Next, the freshly obtained aldehyde (in THF (2 mL)) was slowly added and the mixture was stirred for 2 hours while slowly warming it to room temperature. After this time TLC analysis indicated complete conversion of the aldehyde. EtOAc (20 mL) was added and the mixture was extracted with mM aq. HCl (2×) and brine, dried over MgSO4 and concentrated under reduced pressure. The title compound was obtained after column chromatography (20%→50% EtOAc/PE) as a colourless foam (yield: 0.57 g, 0.95 mmol, 85%). 1H NMR (400 MHz, CDCl3): δ=7.46 (d, J=7.6 Hz, 6H), 7.28 (t, J=7.20, 6.80 Hz, 6H), 7.20 (t, J=7.20, 7.20 Hz, 3H), 7.13 (d, J=7.60 Hz, 2H), 6.87 (d, J=8.00 Hz, 2H), 6.57 (dd, J=14.80, 7.00 Hz, 1H), 5.96 (d, J=14.80 Hz, 1H), 4.80 (s, 1H), 4.24 (d, J=5.60 Hz, 2H), 3.49 (q, J=6.00 Hz, 1H), 2.61 (s, 3H), 2.54 (dd, J=13.20, 5.20 Hz, 1H), 2.33 (dd, J=13.20, 8.20 Hz, 1H), 1.44 (s, 9H) ppm. 13C NMR (100 MHz, CDCl3): δ=155.59, 150.21, 145.74, 137.42, 135.28, 129.53, 128.35, 128.02, 127.70, 127.14, 126.44, 78.91, 71.05, 55.33, 43.79, 42.43, 41.86, 28.09 ppm. [α]D≦=−21.3 (c=1, CHCl3). HRMS: calcd. for C36H40N2O4S 619.26010 [M+Na]+. Found 619.26001.

Source