Tetrahydrofuran → HCID 59830673, compound

HRID 1187365Notes

Reaction equation

HRID 1187365 reaction equation
[CH2:1]1C[O:4][CH2:3][CH2:2]1.Cl[C:7]1[N:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:8]=1[C:9]([NH:11][CH:12]1[CH:19]2[CH2:20][CH:15]3[CH2:16][C:17]([OH:22])([CH2:21][CH:13]1[CH2:14]3)[CH2:18]2)=[O:10]>CCOC(C)=O>[Cl:27][C:25]1[CH:24]=[CH:23][C:8]([C:9]([NH:11][CH:12]2[CH:13]3[CH2:14][CH:15]4[CH2:16][C:17]([OH:22])([CH2:18][CH:19]2[CH2:20]4)[CH2:21]3)=[O:10])=[C:7]([O:4][CH2:3][CH2:2][CH3:1])[N:26]=1

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 59830728HCID 59830728, compound

Product 1

HCID 59830673HCID 59830673, compoundYield 93.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

Bis-sodium hexamethyldisilylamide 1.0M in THF (1 ml, 1 mmol) was added to 2,6-dichloro-N-(5-hydroxyadamantan-2-yl)nicotinamide (341 mg, 1 mmol) and heated at 150° C. for 2 hours. The reaction mixture was diluted with EtOAc (60 mL), and washed sequentially with water (20 mL) and saturated brine (20 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in DCM. Pure fractions were evaporated to dryness to afford 6-chloro-N-(5-hydroxyadamantan-2-yl)-2-propoxynicotinamide (341 mgs, 93%) as a white solid.

Workup

  1. washwashed sequentially with water (20 mL) and saturated brine (20 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in DCM
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-bb32e0c02c984444bbf0029e97424790
Source dataset
uspto-grants-2014_03
Patent number
US08673938B2

Reaction notes

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