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

HRID 1912362Notes

Reaction equation

HRID 1912362 reaction equation
CON(C)[C:4](=O)[C@@H:5]([NH:22][C:23]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:6][C:7]1[CH:21]=[CH:20][C:10]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:9][CH:8]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].Cl.[CH3:51][S:52]([CH2:55]P(=O)(OCC)OCC)(=[O:54])=[O:53].[H-].[Na+]>CCOCC.C1COCC1.CCOC(C)=O>[CH3:51][S:52](/[CH:55]=[CH:4]/[C@@H:5]([NH:22][C:23]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[CH2:6][C:7]1[CH:21]=[CH:20][C:10]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[CH:9][CH:8]=1)(=[O:53])=[O:54]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 533797Diethyl (methanesulfonylmethyl)phosphonateHCID 21226445Aluminium lithium hydrideHCID 71562242(S)-tert-butyl 4-(3-(methoxy(methyl)amino)-3-oxo-2-(tritylamino)propyl)benzylcarbamate

Product 1

HCID 71562243(S,E)-tert-butyl 4-(4-(methylsulfonyl)-2-(tritylamino)but-3-en-1-yl)benzylcarbamate

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

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]D23=−21.3 (c=1, CHCl3). HRMS: calcd. for C36H40N2O4S 619.26010 [M+Na]+. found 619.26001.

Workup

  1. customthe layers were separated
  2. extractionThe organic layer was extracted with 0.1 M aq. HCl and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. temperaturecooled to 0° C. under an argon atmosphere
  6. stirringthe mixture was stirred at 0° C. for 30 minutes
  7. stirringthe mixture was stirred for 2 hours
  8. temperaturewhile slowly warming it to room temperature
  9. extractionthe mixture was extracted with mM aq. HCl (2×) and brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0d9bb2e483ed455292d2474ea27b0eca
Source dataset
uspto-grants-2013_12
Patent number
US08609610B2

Reaction notes

Loading…