Imidazole → HCID 9985234, compound

HRID 1604613Notes

Reaction equation

HRID 1604613 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][C@H:8]1[CH2:30][CH2:29][C@@:28]2([CH3:31])[C:10](=[CH:11][CH2:12][C@@H:13]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:32])[C@H:14]3[CH2:15][CH2:16][C@@H:17]2[C@H:18]([CH3:23])[CH2:19][CH2:20][CH2:21][OH:22])[CH2:9]1.[Si:33](Cl)([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34].N1C=CN=C1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Si:33]([O:22][CH2:21][CH2:20][CH2:19][C@H:18]([C@@H:17]1[C@:24]2([CH3:32])[C@H:14]([C@H:13]3[C@H:27]([CH2:26][CH2:25]2)[C@:28]2([CH3:31])[C:10]([CH2:9][C@@H:8]([O:7][CH:2]4[CH2:3][CH2:4][CH2:5][CH2:6][O:1]4)[CH2:30][CH2:29]2)=[CH:11][CH2:12]3)[CH2:15][CH2:16]1)[CH3:23])([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 516892Sodium BicarbonateHCID 10388777HCID 10388777, compound

Product 1

HCID 9985234HCID 9985234, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Compound 2002 (7.6 g, 17 mmol) in dry CH2Cl2 (300 ml) was treated with a solution of t-butyldimethylsilylchloride (TBDMSCl, 1.0M) and imidazole (0.5M) in dry CH2Cl2 (38.0 ml, 38.0 mmol TBDMSCl). The solution was stirred at room temperature under argon overnight. The resultant solution was poured into an aqueous saturated NaHCO3 solution and the mixture extracted with CH2Cl2 (3×). The combined organic layers were washed with saturated sodium chloride, dried over anhydrous MGSO4, filtered, and the solvent removed in vacuo. The resultant solid was purified by flash chromatography (SiO2, hexanes:EtOAc gradient from 20:1 to 5:1) giving compound 2003 (9.4 g, 17 mmol, 98%). 1H NMR (500 MHz, CDCl3) δ: 5.38-5.32 (m, 1H, C-6 H), 4.72 (brs, 1H, THP methine H), 3.95-3.88 (m, 1H, THP CH2O), 3.60-3.46 (m, 4H THP CH2O & C-3 H & C-24 H), 1.01 (s, 3H, C-19 H), 0.93 (d, J=6.6 Hz, C-21 H), 0.89 (s, 9H, t-Bu), 0.67 (s, 3H, C-18 H), 0.05 (s, 6H, TBDMS CH3); IR (CHCl3) 2900 cm-1 ; MS (CI/isobutane) m/z 559 (M+1, 1%), 474 (M+1-THP, 12%), 457 (M+1-THPOH, 18%), 343 (M+1-THP-TBDMSOH, 6%), 325 (M+1-THPOH-TBDMSOH, 100%); m.p. 116-118° C.; Anal. calcd. for C35H62O3Si: C=75.21, H=11.18; Found: C=75.37, H=11.24.

Workup

  1. extractionthe mixture extracted with CH2Cl2 (3×)
  2. washThe combined organic layers were washed with saturated sodium chloride
  3. customdried over anhydrous MGSO4
  4. filtrationfiltered
  5. customthe solvent removed in vacuo
  6. customThe resultant solid was purified by flash chromatography (SiO2, hexanes:EtOAc gradient from 20:1 to 5:1)

Sources & evidence

ORD record
ord-bc27e4a1fa304a2495001b683ceac49b
Source dataset
uspto-grants-1999_11
Patent number
US05994336

Reaction notes

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