Sodium hydride → HCID 86695145, compound

HRID 1503989Notes

Reaction equation

HRID 1503989 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][C@H:28]1[CH2:39][CH2:38][C:37]2[S:36][C:35]3[N:34]=[CH:33][N:32]=[C:31](Cl)[C:30]=3[C:29]1=2)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]>C1COCC1>[Si:19]([O:26][CH2:27][C@H:28]1[CH2:39][CH2:38][C:37]2[S:36][C:35]3[N:34]=[CH:33][N:32]=[C:31]([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:30]=3[C:29]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 86695146HCID 86695146, compound

Product 1

HCID 86695145HCID 86695145, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (60% dispersion in mineral oil, 240 mg, 6.00 mmol, 3.00 equiv) was treated with tert-butyl N-(4-hydroxycyclohexyl)-N-methylcarbamate (642 mg, 2.80 mmol, 1.40 equiv) in freshly distilled tetrahydrofuran (14 mL) at 0° C. under nitrogen for 30 min. To this mixture was added a solution of (3S)-3-[[(tert-butyldimethylsilyl)oxy]methyl]-12-chloro-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraene (710 mg, 2.00 mmol, 1.00 equiv) in 5 mL of THF via syringe and the resulting solution was stirred overnight at room temperature. After completion, the reaction was quenched with saturated aqueous NH4Cl and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (8:1) to give the desired tert-butyl N-(4-[[(3S)-3-[[(tert-butyldimethylsilyl)oxy]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 (963 mg, 88%) as light yellow oil. MS: m/z 548 (M+H)+.

Workup

  1. customAfter completion, the reaction was quenched with saturated aqueous NH4Cl
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-3affe1f1909b4c619cf42c1cc9958516
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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