Sodium hydride → HCID 117974090, compound

HRID 1776091Notes

Reaction equation

HRID 1776091 reaction equation
[H-].[Na+].[CH2:3]([C@@H:10]([CH:25]=[CH2:26])[C@@H:11]([OH:24])[C@@H:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)[CH3:13])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br[CH2:28][CH2:29][O:30][CH3:31]>CN(C=O)C>[CH2:3]([C@@H:10]([CH:25]=[CH2:26])[C@@H:11]([O:24][CH2:28][CH2:29][O:30][CH3:31])[C@@H:12]([O:14][CH2:15][C:16]1[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=1)[CH3:13])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 809722-Bromoethyl methyl ether2×HCID 117974487HCID 117974487, compound

Product 1

HCID 117974090HCID 117974090, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of NaH (0.088 g, 3.68 mmol) in DMF (10 mL) was added dropwise a solution of (2S,3R,4S)-4-benzyl-2-((4-methoxybenzyl)oxy)hex-5-en-3-ol (1 g, 3.06 mmol) in DMF (5 mL). The mixture was stirred at room temperature for 20 min and then 1-bromo-2-methoxyethane (0.852 g, 6.13 mmol) was added. The reaction mixture was heated to 60° C. for 5 h. The reaction was cooled to room temperature and another portion of NaH (0.088 g, 3.68 mmol) and 1-bromo-2-methoxyethane (0.852 g, 6.13 mmol) were added, and the reaction mixture was heated to 60° C. and stirred overight. The reaction mixture was quenched with saturated NH4Cl and the phases were separated. The aqueous phase was extracted with EtOAc (2×40 mL), and the combined organic phases were dried over MgSO4, concentrated, and purified by column chromatography on SiO2 (EtOAc/hexanes) to furnish the title product as colorless oil (0.730 g, 62%): 1H NMR (400 MHz, CDCl3) δ 7.30-7.06 (m, 7H), 6.86 (dd, J=8.6, 0.9 Hz, 2H), 5.68-5.47 (m, 1H), 4.95-4.69 (m, 2H), 4.60-4.26 (m, 2H), 4.04-3.91 (m, 1H), 3.79 (s, 3H), 3.73-3.69 (m, 1H), 3.68-3.60 (m, 1H), 3.59-3.53 (m, 2H), 3.39 (d, J=0.8 Hz, 3H), 3.38-3.36 (m, 1H), 3.15 (d, J=10.4 Hz, 1H), 2.70-2.42 (m, 2H), 1.30-1.17 (m, 3H); 13C NMR (101 MHz, CDCl3) δ 159.05, 140.67, 138.83, 130.95, 129.56, 129.11, 127.92, 125.60, 116.61, 113.74, 84.59, 76.46, 72.41, 71.76, 70.26, 58.96, 55.28, 48.55, 36.96, 14.01; ESIMS m/z 407.2 ([M+Na]+).

Workup

  1. temperatureThe reaction mixture was heated to 60° C. for 5 h
  2. temperatureThe reaction was cooled to room temperature
  3. temperaturethe reaction mixture was heated to 60° C.
  4. stirringstirred overight
  5. customThe reaction mixture was quenched with saturated NH4Cl
  6. customthe phases were separated
  7. extractionThe aqueous phase was extracted with EtOAc (2×40 mL)
  8. dry with materialthe combined organic phases were dried over MgSO4
  9. concentrationconcentrated
  10. custompurified by column chromatography on SiO2 (EtOAc/hexanes)

Sources & evidence

ORD record
ord-73ce71eb48264d5483963b7894b18593
Source dataset
uspto-grants-2016_02
Patent number
US09265253B2

Reaction notes

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