Sodium hydride → HCID 86695111, compound

HRID 1503937Notes

Reaction equation

HRID 1503937 reaction equation
[OH:1][CH2:2][C@H:3]1[CH2:14][CH2:13][C:12]2[S:11][C:10]3[N:9]=[CH:8][N:7]=[C:6]([O:15][CH:16]4[CH2:21][CH2:20][CH:19]([N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:18][CH2:17]4)[C:5]=3[C:4]1=2.[H-].[Na+].I[CH2:34][CH2:35][O:36][CH2:37][C:38]1[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][CH:39]=1>CN(C=O)C>[CH3:45][O:44][C:41]1[CH:42]=[CH:43][C:38]([CH2:37][O:36][CH2:35][CH2:34][O:1][CH2:2][C@H:3]2[CH2:14][CH2:13][C:12]3[S:11][C:10]4[N:9]=[CH:8][N:7]=[C:6]([O:15][CH:16]5[CH2:17][CH2:18][CH:19]([N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:26])([CH3:27])[CH3:28])[CH2:20][CH2:21]5)[C:5]=4[C:4]2=3)=[CH:39][CH:40]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 11392191HCID 11392191, compoundHCID 68115352HCID 68115352, compound

Product 1

HCID 86695111HCID 86695111, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 50-mL round-bottom flask containing a solution of tert-butyl N-(4-[[(3S)-3-(hydroxymethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (940 mg, 2.17 mmol, 1.00 equiv) in freshly distilled DMF (6 mL) was added sodium hydride (60% dispersion in mineral oil, 347.3 mg) slowly at 0° C. under nitrogen. After the addition, the reaction mixture was stirred at room temperature for 30 min. Then 1-[(2-iodoethoxy)methyl]-4-methoxybenzene (2.535 g, 8.68 mmol, 4.00 equiv) was added to the mixture and stirred for 14 hrs at ambient temperature. The reaction was quenched slowly with saturated aqueous NH4Cl and extracted with 3×100 mL of ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5) to give tert-butyl N-(4-[[(3S)-3-([2-[(4-methoxyphenyl)methoxy]ethoxy]methyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (700 mg, 54%) as a colorless oil. MS: m/z 598 (M+H)+.

Workup

  1. additionAfter the addition
  2. stirringstirred for 14 hrs at ambient temperature
  3. customThe reaction was quenched slowly with saturated aqueous NH4Cl
  4. extractionextracted with 3×100 mL of ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f5c3269f3ae94191b8be7fb8625d856c
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

Loading…