Isobutyryl chloride → HCID 118194689, compound

HRID 1770379Notes

Reaction equation

HRID 1770379 reaction equation
[CH2:1]([C@H:5]1[C@H:13]([CH3:14])[O:12][C:11](=[O:15])[C@@H:10]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:9][CH2:8][CH2:7][C@@H:6]1[OH:24])[CH2:2][CH2:3][CH3:4].[C:25](Cl)(=[O:29])[CH:26]([CH3:28])[CH3:27]>N1C=CC=CC=1.CN(C1C=CN=CC=1)C>[C:25]([O:24][C@H:6]1[CH2:7][CH2:8][CH2:9][C@H:10]([NH:16][C:17]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:23])[C:11](=[O:15])[O:12][C@@H:13]([CH3:14])[C@@H:5]1[CH2:1][CH2:2][CH2:3][CH3:4])(=[O:29])[CH:26]([CH3:28])[CH3:27]

Participants

5

Reactant 2

HCID 62325Isobutyryl chloride2×HCID 118199353HCID 118199353, compound

Product 1

HCID 118194689HCID 118194689, compoundYield 56.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of tert-butyl ((3S,7S,8R,9S)-8-butyl-7-hydroxy-9-methyl-2-oxooxonan-3-yl)carbamate (0.405 g, 1.179 mmol) in pyridine (3.4 mL) was added DMAP (0.029 g, 0.236 mmol) followed by the slow addition of isobutyryl chloride (0.247 ml, 2.36 mmol) at room temperature. The reaction was warmed to 50° C. and stirred for 3 h, at which point additional isobutyryl chloride (0.247 ml, 2.36 mmol) was added. The reaction was stirred at 50° C. for an additional 14 h, cooled to room temperature, quenched with sat. aq. NH4Cl (5 ml), and extracted with EtOAc (3×10 ml). The combined organic extracts were dried over MgSO4, filtered, and concentrated to dryness. The crude residue was purified by flash chromatography (SiO2; EtOAc/hexanes) to give the title compound (0.274 g, 0.663 mmol, 56%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 5.15 (d, J=8.3 Hz, 1H), 4.91-4.84 (m, 1H), 4.79 (dq, J=10.0, 6.3 Hz, 1H), 4.27-4.16 (m, 1H), 2.60-2.44 (m, 1H), 2.23 (dt, J=13.8, 7.1 Hz, 1H), 2.15-1.99 (m, 3H), 1.73 (tdd, J=13.0, 7.3, 2.3 Hz, 1H), 1.57-1.46 (m, 1H), 1.44 (s, 9H), 1.34 (d, J=6.4 Hz, 4H), 1.33-1.19 (m, 5H), 1.18-1.12 (m, 6H), 1.04-0.94 (m, 1H), 0.87 (t, J=7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 175.41, 172.91, 154.98, 79.76, 74.44, 73.12, 52.42, 45.44, 34.24, 33.73, 33.32, 30.88, 28.29, 27.38, 23.25, 19.19, 19.03, 18.88, 18.79, 18.02, 13.82; ESIMS m/z 436 ([M+Na]+).

Workup

  1. additionwas added
  2. temperaturecooled to room temperature
  3. customquenched with sat. aq. NH4Cl (5 ml)
  4. extractionextracted with EtOAc (3×10 ml)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe crude residue was purified by flash chromatography (SiO2; EtOAc/hexanes)

Sources & evidence

ORD record
ord-f48f6d42cbc04a629f7983e146febb48
Source dataset
uspto-grants-2016_02
Patent number
US09247741B2

Reaction notes

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