Sodium hydride → HCID 86701097, compound

HRID 1396236Notes

Reaction equation

HRID 1396236 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]1[O:18][C@H:17]2[C@H:13]([N:14]=[C:15]([N:19]([CH2:27][CH2:28][CH3:29])[C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[S:16]2)[C@@H:12]([OH:30])[C@@H:11]1[OH:31])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=1>CN(C=O)C>[Si:1]([O:8][CH2:9][C@H:10]1[O:18][C@H:17]2[C@H:13]([N:14]=[C:15]([N:19]([CH2:27][CH2:28][CH3:29])[C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:25])[CH3:24])[S:16]2)[C@@H:12]([O:30][CH2:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)[C@@H:11]1[O:31][CH2:35][C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=1)([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1650214-Methoxybenzyl bromideHCID 86701096HCID 86701096, compound

Product 1

HCID 86701097HCID 86701097, compoundYield 66.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl (3aR,5R,6S,7R,7aR)-5-((tert-butyldimethylsilyloxy)methyl)-6,7-dihydroxy-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl(propyl)carbamate (20 g, 42 mmol) in DMF (300 mL) was added sodium hydride (10 g, 417 mmol) at 15° C. in portions, followed by addition of 1-(bromomethyl)-4-methoxybenzene (33.8 g, 168 mmol). The resulting solution was stirred for 1.5 h at room temperature, quenched by addition of cold water (100 mL), and extracted with dichloromethane (5×100 mL). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated under vacuum to provide a residue, which was purified by silica gel column, eluted with 10-25% ethyl acetate in petroleum ether to give compound 18 as a yellow oil (20 g, 64.8%). (ES, m/z): 717.1; 1H NMR (300 MHz, CDCl3) δ 7.32-7.35 (d, J=8.7 Hz, 2H), 7.19-7.22 (d, J=8.7 Hz, 2H), 6.83-6.92 (m. 4H), 6.05-6.07 (d, J=6.9 Hz, 1H), 4.57-4.74 (m, 3H), 4.30-4.39 (m, 2H), 4.14-4.17 (t, J=4.2 Hz, 1H), 3.68-3.84 (m, 11H), 3.41-3.45 (m, 1H), 1.67-1.74 (m, 2H), 1.53 (s, 9H), 0.89 (s, 9H), 0.84 (m, 3H), 0.08 (s, 6H).

Workup

  1. customquenched by addition of cold water (100 mL)
  2. extractionextracted with dichloromethane (5×100 mL)
  3. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under vacuum
  5. customto provide a residue, which
  6. customwas purified by silica gel column
  7. washeluted with 10-25% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-a1891bfe267648d9b2a6044760b02250
Source dataset
uspto-grants-2014_12
Patent number
US08901087B2

Reaction notes

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