Dimethylformamide → HCID 10462082, compound

HRID 357275Notes

Reaction equation

HRID 357275 reaction equation
CN(C=O)C.[Si:6]([O:13][CH2:14][CH2:15][CH2:16][C@H:17]([C@@H:19]1[C@:36]2([CH3:37])[C@H:22]([C@H:23]3[C@H:33]([CH2:34][CH2:35]2)[C@:31]2([CH3:32])[C@H:26]([CH2:27][C@@H:28]([O:38][CH:39]4[CH2:44][CH2:43][CH2:42][CH2:41][O:40]4)[CH2:29][CH2:30]2)[CH2:25][C@H:24]3[OH:45])[CH2:21][CH2:20]1)[CH3:18])([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].[CH2:46](Br)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>C1COCC1>[CH2:46]([O:45][C@@H:24]1[CH2:25][C@@H:26]2[C@:31]([CH3:32])([CH2:30][CH2:29][C@H:28]([O:38][CH:39]3[CH2:44][CH2:43][CH2:42][CH2:41][O:40]3)[CH2:27]2)[C@@H:33]2[C@@H:23]1[C@H:22]1[C@:36]([CH3:37])([CH2:35][CH2:34]2)[C@@H:19]([C@H:17]([CH3:18])[CH2:16][CH2:15][CH2:14][O:13][Si:6]([C:9]([CH3:10])([CH3:11])[CH3:12])([CH3:8])[CH3:7])[CH2:20][CH2:21]1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 7498Benzyl BromideHCID 10348167HCID 10348167, compound

Product 1

HCID 10462082HCID 10462082, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
400 °C

Procedure

A flame-dried round-bottom flask with stirring bar was charged with sodium hydride (60% in mineral oil, 28 mg, 0.69 mmol), equipped with a septum and a gas-needle inlet and flushed with argon. The mineral oil was removed by washing (3×) with dry pentane, and the pentane was removed to provide the sodium hydride as a powder. Dry DMF (2.0 ml) was added. A solution of alcohol 2006 (40 mg, 0.069 mmol) in dry THF (2 ml) was added dropwise via syringe. The reaction mixture was stirred overnight and then heated to 400° C. in an oil bath over a 20-minute period. Freshly distilled benzyl bromide (0.165 ml, 1.38 mmol) was added dropwise, and the reaction mixture was stirred at 400° C. for 10 hours. The reaction was allowed to cool to room temperature, and the solvent was removed under reduced pressure. The flask was placed under vacuum overnight to remove any residual DMF. The crude material was purified by flash chromatography (SiO2, hexanes:EtOAc 50:1) giving compound 2007 as a white solid (40 mg, 0.060 mmol, 87%). A gradient of increasing EtOAc concentration provided other components, including the 7α-formate (1 mg, 1%) as well as recovered starting material (3 mg, 8%). Compound 2007:=1H NMR (500 MHz, CDCl3) δ 7.35-7.20 (m, 5 H, benzyl Ar-CH2), 4.73-4.66 (m, 1 H, methine H), 4.535 (d, J=12.0 Hz, 1/2 H, benzyl-CH2) , 4.53 (d, J=12.0 Hz, 1/2 H, benzyl-CH2), 4.26 (d, J=12.2 Hz, 1/2 H, benzyl-CH2), 4.245 (d, J=11.8 Hz, 1/2 H, benzyl-CH2), 3.95-3.85 (m, 1 H, THP CH2O), 3.66-3.52 (m, 3 H, THP CH2O & C-24 H), 3.50-3.45 (m, 1 H, C-3 H), 1.08 (s, 3 H, C-19 H), 0.91 (d, J=6.6 Hz, C-21 H), 0.89 (s, 9H, t-Bu), 0.64 (s, 3 H, C-18 H), 0.04 (s, 6 H, TBDMS CH3); MS (CI/isobutane) m/z 668 (M+1, 6%), 584 (M+1-THP, 18%), 475 (M+1-THPOH, 30%), 457 (M+1-THPOH-HOBn, 58%), 343 (M+1-THP-HOBn-TBDMSOH, 100%), 325 (M+1-THPOH-TBDMSOH-HOBn, 83%).

Workup

  1. stirringthe reaction mixture was stirred at 400° C. for 10 hours
  2. temperatureto cool to room temperature
  3. customthe solvent was removed under reduced pressure
  4. customwas placed under vacuum overnight
  5. customto remove any residual DMF
  6. customThe crude material was purified by flash chromatography (SiO2, hexanes:EtOAc 50:1)

Sources & evidence

ORD record
ord-838b0647efe24eefb7ef224ded45af8d
Source dataset
uspto-grants-1998_11
Patent number
US05840740

Reaction notes

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