Methyl iodide → HCID 66588570, compound

HRID 1092432Notes

Reaction equation

HRID 1092432 reaction equation
[H-].[Na+].[CH2:3]([O:10][C@H:11]1[C@H:16]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C@@H:15]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C@H:14]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]3[CH:46]=[CH:45][C:44]([CH2:47][CH3:48])=[CH:43][CH:42]=3)[CH:34]=2)[C@@H:13]([OH:49])[C@@H:12]1[CH2:50][O:51][CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.CI.[NH4+].[Cl-].Cl[C:64]1C=CC([C@@H]2[C@@H](OC)[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)=CC=1CC1C=CC(CC)=CC=1>C1COCC1.CCCC[N+](CCCC)(CCCC)CCCC.[I-]>[CH2:26]([O:25][C@@H:15]1[C@@H:16]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C@H:11]([O:10][CH2:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[C@@H:12]([CH2:50][O:51][CH2:52][C:53]2[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=2)[C@H:13]([O:49][CH3:64])[C@H:14]1[C:33]1[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]2[CH:42]=[CH:43][C:44]([CH2:47][CH3:48])=[CH:45][CH:46]=2)[CH:34]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

8

Reactant 5

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 57741114HCID 57741114, compoundHCID 66588466HCID 66588466, compound

Product 1

HCID 66588570HCID 66588570, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

NaH (157 g, 1.5 eq, 60% containing in oil) was added into the solution of (1R,2S,3R,4R,5S,6R)-3,4,5-tris(benzyloxy)-2-(benzyloxymethyl)-6-(4-chloro-3-(4-ethylbenzyl)phenyl)cyclohexanol (4, R=Et, 2 g, 2.61 mmol) in anhydrous THF (10 mL) at 0° C. TBAI (0.1 eq) and CH3I (760 mg, 2 eq) were added into the reaction mixture after stirring for 1 h at the same temperature and the reaction mixture was stirred overnight at rt. Sat aq. NH4Cl was added to quench the reaction and the resulting mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and the filtrate was evaporated to dryness. The residue (yellow oil, 2.05 g) was dissolved in THF:CH3OH=2:1, treated with 1,2-dichlorobenzene (1% mol ratio) and Pd/C (10%, 1/1 weight ratio), and stirred over 2 h under H2 atmosphere at room temperature. The reaction was monitored by LC-MS until completion. The mixture was filtered, and the filtrate was evaporated to dryness and purified by preparative HPLC to give target compound 16 (987 mg, (white solid, yield of 90.0%). 1H-NMR (400 MHz, CD3COCD3): δ 7.32-7.34 (2H, m), 7.22 (1H, dd, J=2.4, 8.0 Hz), 7.12 (4H, dd, J=8.4 Hz), 4.15 (2H, s), 3.93-3.98 (1H, m), 3.70-.3.75 (1H,m), 3.65-3.67 (1H, m), 3.54-3.60 (2H, m), 3.37 (1H, t, J=10.4 Hz), 3.30 (1H, t, J=8.8 Hz), 2.84 (3H, s), 2.52-2.65 (3H, m), 1.51-1.58 (1H, m), 1.17 (3H, t, J=7.2 Hz); MS (ESI+): 421 [M+H]+, 438 [M+NH4]+, 841 [2M+H]+, 858 [2M+NH4]+, (ESI+): 465 [M+HCOO]−.

Workup

  1. stirringthe reaction mixture was stirred overnight at rt
  2. customto quench
  3. customthe reaction
  4. extractionthe resulting mixture was extracted with EtOAc
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. customthe filtrate was evaporated to dryness
  8. dissolutionThe residue (yellow oil, 2.05 g) was dissolved in THF
  9. additionCH3OH=2:1, treated with 1,2-dichlorobenzene (1% mol ratio) and Pd/C (10%, 1/1 weight ratio)
  10. stirringstirred over 2 h under H2 atmosphere at room temperature
  11. filtrationThe mixture was filtered
  12. customthe filtrate was evaporated to dryness
  13. custompurified by preparative HPLC
  14. customto give

Sources & evidence

ORD record
ord-b2f64ed3a66e4147b6ccf09ac3a16a8c
Source dataset
uspto-grants-2012_03
Patent number
US08129434B2

Reaction notes

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