Water → HCID 23574468, compound

HRID 1830945Notes

Reaction equation

HRID 1830945 reaction equation
[CH3:1][O:2][C:3]1[C:8]2[C:9](=[O:26])[N:10]3[CH2:17][C@H:16]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH2:15][C@H:11]3[C:12](=[O:14])[NH:13][C:7]=2[CH:6]=[CH:5][C:4]=1[O:27][CH3:28].[H-].[Na+].[CH3:31][Si:32]([CH2:35][CH2:36][O:37][CH2:38]Cl)([CH3:34])[CH3:33].O>CN(C=O)C>[CH3:1][O:2][C:3]1[C:8]2[C:9](=[O:26])[N:10]3[CH2:17][C@H:16]([O:18][Si:19]([C:22]([CH3:24])([CH3:25])[CH3:23])([CH3:20])[CH3:21])[CH2:15][C@H:11]3[C:12](=[O:14])[N:13]([CH2:38][O:37][CH2:36][CH2:35][Si:32]([CH3:34])([CH3:33])[CH3:31])[C:7]=2[CH:6]=[CH:5][C:4]=1[O:27][CH3:28]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 21034347HCID 21034347, compound

Product 1

HCID 23574468HCID 23574468, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 171 (6.50 g, 15.99 mmol) in anhydrous DMF (27.5 mL) was added dropwise to a stirred suspension of NaH (0.422 g, 0.704 g of a 60% dispersion in mineral oil, 18.34 mmol) at 0° C. and the reaction mixture was allowed to stir for 30 minutes. A solution of SEM chloride (3.11 mL, 2.93 g, 17.59 mmol) in anhydrous DMF (5 mL) was added dropwise to the stirred reaction mixture at 0° C. and allowed to stir at room temperature for 16 h. The reaction mixture was poured into water (200 mL) to afford a white precipitate, which was extracted with diethyl ether (4×300 mL). The organic layer was washed with water (2×50 mL), brine (2×50 mL) and dried over anhydrous MgSO4. Filtration and evaporation of the solvent in vacuo afforded the crude product, which was purified by flash column chromatography using an 80:20 mixture of petroleum ether:EtOAc as eluent. Pure fractions were combined and evaporated in vacuo to afford the product (172) as a yellow oil (7.01 g, 13.1 mmol, 82%). 1H NMR (270 MHz, CDCl3) δ7.35 (s, 1H, ArH), 7.24 (s, 1H, ArH), 5.52 (d, 2H, J=9.89 Hz, SEM amino acetal CH2), 4.65 (d, 2H, J=9.90 Hz, SEM amino acetal CH2), 4.61-4.56 (m, 1H, 2), 4.23 (dd, 1H, J=4.40 Hz, 8.24 Hz, 11a), 3.94 (s, 3H, OMe), 3.92 (s, 3H, OMe), 3.68 (m, 4H, SEM 1′ CH2+3), 2.86 (m, 1H, 1), 2.02 (m, 1H, 1), 0.98 (t, 2H, J=8.25 Hz, SEM 2′ CH2), 0.88 (s, 9H, TBDMS t-Bu CH3), 0.10 (s, 6H, 2×TBDMS SiCH3), 0.03 (s, 9H, 3× SEM SiCH3); 13C NMR (67.8 MHz, CDCl3) δ170.0, 165.6, 151.8, 147.1, 133.9, 121.5, 111.2, 105.5, 78.1, 69.6, 67.0, 56.5, 56.2, 56.1, 53.6, 35.5, 25.7, 18.4, −1.3, −4.8.

Workup

  1. stirringto stir at room temperature for 16 h
  2. customto afford a white precipitate, which
  3. extractionwas extracted with diethyl ether (4×300 mL)
  4. washThe organic layer was washed with water (2×50 mL), brine (2×50 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationFiltration and evaporation of the solvent in vacuo
  7. customafforded the crude product, which
  8. customwas purified by flash column chromatography
  9. additionan 80:20 mixture of petroleum ether
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-0e56dd39f2f3460abcbeba34396730f3
Source dataset
uspto-grants-2006_06
Patent number
US07067511B2

Reaction notes

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