Sodium hydride → HCID 86695178, compound

HRID 1504021Notes

Reaction equation

HRID 1504021 reaction equation
[H-].[Na+].[OH:3][C@H:4]1[CH2:9][CH2:8][C@H:7]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:6][CH2:5]1.[Si:18]([O:25][CH2:26][CH2:27][C@H:28]1[CH2:40][C:39]2[C:38]3[C:37](Cl)=[N:36][CH:35]=[N:34][C:33]=3[S:32][C:31]=2[CH2:30][CH2:29]1)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]>C1COCC1>[Si:18]([O:25][CH2:26][CH2:27][C@H:28]1[CH2:40][C:39]2[C:38]3[C:37]([O:3][CH:4]4[CH2:9][CH2:8][CH:7]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:14])([CH3:16])[CH3:15])[CH2:6][CH2:5]4)=[N:36][CH:35]=[N:34][C:33]=3[S:32][C:31]=2[CH2:30][CH2:29]1)([C:21]([CH3:24])([CH3:22])[CH3:23])([CH3:19])[CH3:20]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86695175HCID 86695175, compoundHCID 178418329HCID 178418329, compound

Product 1

HCID 86695178HCID 86695178, compoundYield 68.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (60% dispersion in mineral oil, 62 mg, 1.55 mmol, 30.00 equiv) was treated with tert-butyl trans-N-(4-hydroxycyclohexyl)carbamate (157 mg, 0.73 mmol, 1.40 equiv) in 8 mL of freshly distilled THF for 30 min in a water/ice bath under nitrogen. Then a solution of (12R)-12-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-3-chloro-8-thia-4,6-diazatricyclo[7.4.0.0[2,7]]trideca-1(9),2(7),3,5-tetraene (200 mg, 0.52 mmol, 1.00 equiv) in 5 mL of THF was added via syringe and the mixture was stirred at room temperature overnight. The reaction was quenched with saturated aqueous NH4Cl and extracted with 3×50 mL of ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:4) to give tert-butyl N-(4-[[(12R)-12-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-8-thia-4,6-diazatricyclo[7.4.0.0[2,7]]trideca-1(9),2(7),3,5-tetraen-3-yl]oxy]cyclohexyl)carbamate (200 mg, 68%) as a yellow oil.

Workup

  1. customThe reaction was quenched with saturated aqueous NH4Cl
  2. extractionextracted with 3×50 mL of ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d398bbe32c444594b1834ab9435180b8
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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