Sodium hydride → HCID 86619884, compound

HRID 2388816Notes

Reaction equation

HRID 2388816 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]2)[O:4][CH2:3][C@@H:2]1[C@@H:11]([OH:13])[CH3:12].[H-].[Na+].[Cl:16][C:17]1[CH:22]=[C:21](Cl)[N:20]=[C:19]([S:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=2[F:33])[N:18]=1>C1COCC1>[Cl:16][C:17]1[CH:22]=[C:21]([O:13][C@H:11]([C@H:2]2[CH2:3][O:4][C:5]3([CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]3)[O:1]2)[CH3:12])[N:20]=[C:19]([S:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=2[F:33])[N:18]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10103902HCID 10103902, compoundHCID 859280374,6-Dichloro-2-((2,3-difluorobenzyl)thio)pyrimidine

Product 1

HCID 86619884HCID 86619884, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (1S)-1-[(2R)-1,4-dioxaspiro[4.5]dec-2-yl]ethanol (prepared according to J. Org. Chem. 1995, 60, 585-587, 0.183 g of −2:1 mixture of diastereomers) in dry THF (5 ml) was cooled to 0° C. and to it was added (in portions) sodium hydride (46 mg as 60% dispersion in mineral oil) followed in portions by 4,6-dichloro-2-(2,3-difluoro-benzylsulfanyl)-pyrimidine (product of example 1 step ii, 0.252 g). The reaction mixture was stirred at room temperature for 24 h then quenched with saturated aqueous ammonium chloride (2 ml) and diluted with EtOAc. The layers were separated and the aqueous layer extracted with further EtOAc. The combined organic extracts were washed with saturated aqueous sodium chloride, dried with sodium sulfate, filtered and evaporated to leave a yellow oil which was purified by column chromatography on silica using a 0.5 to 4% mixture of EtOAc in iso-hexane as eluent to afford the subtitle compound as a white solid. Yield: 0.10 g

Workup

  1. customthen quenched with saturated aqueous ammonium chloride (2 ml)
  2. additiondiluted with EtOAc
  3. customThe layers were separated
  4. extractionthe aqueous layer extracted with further EtOAc
  5. washThe combined organic extracts were washed with saturated aqueous sodium chloride
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customto leave a yellow oil which
  10. customwas purified by column chromatography on silica using a 0.5 to 4% mixture of EtOAc in iso-hexane as eluent

Sources & evidence

ORD record
ord-4b578b094b574fb1a64516f84e6ed14a
Source dataset
uspto-grants-2012_09
Patent number
US08269002B2

Reaction notes

Loading…