Sodium hydride → HCID 131735326, compound

HRID 627632Notes

Reaction equation

HRID 627632 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH3:31])[N:17]=[C:16]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C:12]3([CH2:15][CH2:14][CH2:13]3)[S:11](=[O:27])(=[O:26])[C@@H:10]2[CH2:28][CH2:29][OH:30])[C:5](F)=[N:6][CH:7]=1.[H-].[Na+]>C1COCC1.CN(C=O)C>[Br:1][C:2]1[CH:7]=[N:6][C:5]2[O:30][CH2:29][CH2:28][C@H:10]3[C@@:9]([CH3:31])([C:4]=2[CH:3]=1)[N:17]=[C:16]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C:12]1([CH2:15][CH2:14][CH2:13]1)[S:11]3(=[O:27])=[O:26]

Participants

4

Reactant 2

HCID 24758Sodium hydride2×HCID 86728106HCID 86728106, compound

Product 1

HCID 131735326HCID 131735326, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

A solution of tert-butyl ((6R,7R)-7-(5-bromo-2-fluoropyridin-3-yl)-6-(2-hydroxyethyl)-7-methyl-5,5-dioxido-5-thia-8-azaspiro[3.5]non-8-en-9-yl)carbamate (1.04 g, 1.998 mmol) in THF/DMF (20/2 mL) was brought to 0° C. followed by the addition of sodium hydride, 60% dispersion in mineral oil (0.200 g, 5.00 mmol) in one portion. After one min stirring at 0° C. the ice bath was removed. The reaction became yellow. More sodium hydride, 60% dispersion in mineral oil (0.200 g, 5.00 mmol) was added at rt and stirred for 20 min more. The reaction went to completion (3:1 mixture of epimers). The mixture was brought to 0° C. and carefully quenched with saturated NH4Cl and water was added. The reaction mixture was extracted with EtOAc and the combined organics were dried over Na2SO4, filtered, concentrated and chromatographed on silica gel using 0-30% EtOAc/hexanes to afford each isomer as a white solid tert-butyl ((4a′S,11b′R)-10′-bromo-11b′-methyl-4′,4′-dioxido-4a′,5′,6′,11b′-tetrahydrospiro[cyclobutane-1,3′-pyrido[3′,2′:6,7]oxepino[4,5-b][1,4]thiazin]-2′-yl)carbamate (0.46 g, 0.919 mmol, 46.0% yield). LC/MS (ESI+) m/z=521.8 (M+H).

Workup

  1. customwas brought to 0° C.
  2. customwas removed
  3. additionThe reaction went to completion (3:1 mixture of epimers)
  4. customwas brought to 0° C.
  5. customcarefully quenched with saturated NH4Cl and water
  6. additionwas added
  7. extractionThe reaction mixture was extracted with EtOAc
  8. dry with materialthe combined organics were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customchromatographed on silica gel using 0-30% EtOAc/hexanes

Sources & evidence

ORD record
ord-81f527b049534ca4a68ea245f71ae206
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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