Sodium hydride → HCID 86695210, compound

HRID 1504053Notes

Reaction equation

HRID 1504053 reaction equation
[CH2:1]1[C:4]2([CH2:7][N:6]([CH:8]3[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]3)[CH2:5]2)[CH2:3][O:2]1.[H-].[Na+].[Si:17]([O:24][CH2:25][C@H:26]1[CH2:37][CH2:36][C:35]2[S:34][C:33]3[C:28](=[C:29](Cl)[N:30]=[CH:31][N:32]=3)[C:27]1=2)([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]>C1COCC1>[Si:17]([O:24][CH2:25][C@H:26]1[CH2:37][CH2:36][C:35]2[S:34][C:33]3[C:28](=[C:29]([O:14][CH:11]4[CH2:10][CH2:9][CH:8]([N:6]5[CH2:7][C:4]6([CH2:1][O:2][CH2:3]6)[CH2:5]5)[CH2:13][CH2:12]4)[N:30]=[CH:31][N:32]=3)[C:27]1=2)([C:20]([CH3:23])([CH3:21])[CH3:22])([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86695146HCID 86695146, compoundHCID 86695209HCID 86695209, compound

Product 1

HCID 86695210HCID 86695210, compoundYield 91.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-[2-oxa-6-azaspiro[3.3]heptan-6-yl]cyclohexan-1-ol (250 mg, 1.27 mmol, 1.19 equiv) in 15 mL of freshly distilled THF was added sodium hydride (60% dispersion in mineral oil, 169.9 mg, 4.25 mmol, 4.00 equiv) in portions at 0° C. under nitrogen. The resulting solution was stirred for 0.5 h at this temperature. Then (3S)-3-[[(tert-butyldimethylsilyl)oxy]methyl]-12-chloro-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraene (377 mg, 1.06 mmol, 1.00 equiv) was added and the resulting solution was allowed to react, with stirring, for an additional 2 h at ambient temperature. After completion of the reaction, the reaction mixture was quenched by the addition of 20 mL of saturated aqueous NH4Cl and extracted with 3×50 mL of ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate to give the desired (3S)-3-[[(tert-butyldimethylsilyl)oxy]methyl]-12-[(4-[2-oxa-6-azaspiro[3.3]heptan-6-yl]cyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraene (0.5 g, 91%) as a colorless oil.

Workup

  1. customto react
  2. stirringwith stirring, for an additional 2 h at ambient temperature
  3. customAfter completion of the reaction
  4. customthe reaction mixture was quenched by the addition of 20 mL of saturated aqueous NH4Cl
  5. extractionextracted with 3×50 mL of ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-6724caac4565451fa6e2791b44bf7848
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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