Allyl bromide → (2R,3S)-Diisopropyl 2-(allyloxy)-3-((6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridin-2-yl)methyl)succinate

HRID 73483Notes

Reaction equation

HRID 73483 reaction equation
[CH3:1][C:2]1[N:3]([C:8]2[N:13]=[C:12]([CH2:14][C@@H:15]([C@@H:22]([OH:29])[C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[C:16]([O:18][CH:19]([CH3:21])[CH3:20])=[O:17])[CH:11]=[C:10]([CH3:30])[CH:9]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1.[H-].[Na+].[CH2:33](Br)[CH:34]=[CH2:35]>C1COCC1>[CH2:35]([O:29][C@H:22]([C@H:15]([CH2:14][C:12]1[CH:11]=[C:10]([CH3:30])[CH:9]=[C:8]([N:3]2[C:4]([CH3:7])=[CH:5][CH:6]=[C:2]2[CH3:1])[N:13]=1)[C:16]([O:18][CH:19]([CH3:21])[CH3:20])=[O:17])[C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[CH:34]=[CH2:33]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 24758Sodium hydrideHCID 44543304(2S,3R)-Diisopropyl 2-((6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridin-2-yl)methyl)-3-hydroxysuccinate

Product 1

HCID 89419083(2R,3S)-Diisopropyl 2-(allyloxy)-3-((6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridin-2-yl)methyl)succinateYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of alcohol 4b (300 mg, 0.72 mmol) in THF (10 mL) at 0° C. was added NaH (60% in mineral oil, 35 mg, 0.87 mmol). The mixture was allowed to stir at 0° C. for an additional 30 min then allyl bromide (93 μL, 1.08 mmol) was added dropwise. The reaction was allowed to warm to room temperature and maintained for an additional 6 h. The reaction was quenched with saturated NH4Cl (1 mL) and partitioned between EtOAc (100 mL) and H2O (50 mL). The organic layer was washed with brine (50 mL) and dried over Na2SO4. The solvent was removed by rotary evaporation, the resulting brown oil was purified by flash column chromatography (EtOAc/hexanes, 1:9-1:1) to give 10 (316 mg, 0.69 mmol, 97%) as a pale yellow oil: 1H NMR (500 MHz, CDCl3) δ 1.07-1.09 (d, J=6.0 Hz, 3H), 1.16-1.19 (d, J=6.0 Hz, 3H), 1.25-1.35 (m, 6H), 2.13 (s, 6H), 2.39 (s, 3H), 3.01-3.05 (dd, J=5.5, 15.5 Hz, 1H), 3.20-3.25 (dd, J=9.5, 15.0 Hz, 1H), 3.67-3.68 (dd, J=3.0, 4.5 Hz, 1H), 3.89-3.94 (dd, J=7.0, 13.0 Hz, 1H), 4.02-4.03 (d, J=5.0 Hz, 1H), 4.24-4.28 (dd, J=4.5, 12.0 Hz, 1H), 4.93-4.96 (m, 1H), 4.97-5.17 (m, 1H), 5.17-5.19 (d, J=10.0 Hz, 1H), 5.25-5.29 (dd, J=1.5, 17.0 Hz, 1H), 5.80-5.95 (m, 3H), 6.86 (s, 1H), 7.02 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 13.6, 21.2, 21.8, 21.9, 22.0, 22.1, 35.6, 47.7, 68.5, 68.9, 72.1, 78.1, 106.9, 118.0, 120.4, 123.7, 128.7, 134.2, 149.7, 151.8, 158.8, 170.4, 171.2; LCQ-MS (M+H+) calcd for C26H37N2O5 457. found 457; LC-TOF-MS (M+H+) calcd for C26H37N2O5 457.27025. found 457.26984.

Workup

  1. temperatureto warm to room temperature
  2. temperaturemaintained for an additional 6 h
  3. customThe reaction was quenched with saturated NH4Cl (1 mL)
  4. custompartitioned between EtOAc (100 mL) and H2O (50 mL)
  5. washThe organic layer was washed with brine (50 mL)
  6. dry with materialdried over Na2SO4
  7. customThe solvent was removed by rotary evaporation
  8. customthe resulting brown oil was purified by flash column chromatography (EtOAc/hexanes, 1:9-1:1)

Sources & evidence

ORD record
ord-19fa2039e4a748f9885ad5d0d013bb8f
Source dataset
uspto-grants-2014_09
Patent number
US08829187B1

Reaction notes

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