Sodium hydride → tert-butyl N-(4-[[(3S)-3-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-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

HRID 1503902Notes

Reaction equation

HRID 1503902 reaction equation
[H-].[Na+].[OH:3][CH:4]1[CH2:9][CH2:8][CH:7]([N:10]([CH3:18])[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:6][CH2:5]1.[Si:19]([O:26][CH2:27][CH2:28][C@@H:29]1[CH2:40][CH2:39][C:38]2[S:37][C:36]3[N:35]=[CH:34][N:33]=[C:32](Cl)[C:31]=3[C:30]1=2)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]>C1COCC1>[Si:19]([O:26][CH2:27][CH2:28][C@@H:29]1[CH2:40][CH2:39][C:38]2[S:37][C:36]3[N:35]=[CH:34][N:33]=[C:32]([O:3][CH:4]4[CH2:9][CH2:8][CH:7]([N:10]([CH3:18])[C:11](=[O:17])[O:12][C:13]([CH3:14])([CH3:15])[CH3:16])[CH2:6][CH2:5]4)[C:31]=3[C:30]1=2)([C:22]([CH3:25])([CH3:23])[CH3:24])([CH3:21])[CH3:20]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 219251474-(N-Boc-N-methylamino)cyclohexanolHCID 86695085(3S)-3-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-12-chloro-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraene

Product 1

HCID 86695084tert-butyl N-(4-[[(3S)-3-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2 (6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamateYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

Sodium hydride (60% dispersion in mineral oil, 1.96 g, 49.00 mmol, 4.02 equiv) was treated with tert-butyl N-(4-hydroxycyclohexyl)-N-methylcarbamate (3.92 g, 17.09 mmol, 1.40 equiv) in distilled THF (50 mL) at 0° C. for 1 h under nitrogen. Then a solution of 22.1 (4.5 g, 12.20 mmol, 1.00 equiv) in 15 mL of THF was added to the reaction mixture, which was stirred for a further 2 h at 60° C. The reaction was then quenched by the addition of 20 mL of water at 0° C. and extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine and dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was loaded onto a silica gel column with ethyl acetate/petroleum ether (1:5) and purified to afford tert-butyl N-(4-[[(3S)-3-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-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 (22.2, 6.5 g, 95%) as yellow oil. MS: m/z 562 (M+H)+.

Workup

  1. customThe reaction was then quenched by the addition of 20 mL of water at 0° C.
  2. extractionextracted with ethyl acetate (3×100 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationAfter filtration and concentration under reduced pressure
  6. custompurified

Sources & evidence

ORD record
ord-a710a829dc6f4cfa954a179812fde422
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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