Sodium Carbonate → 3-[6-Chloro-2-(4-nitro-phenyl)-pyrimidin-4-yl]-8-oxa-3-aza-bicyclo[3.2.1]octane

HRID 75414

Reaction equation

HRID 75414 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](I)[N:5]=[C:4]([N:9]2[CH2:15][CH:14]3[O:16][CH:11]([CH2:12][CH2:13]3)[CH2:10]2)[CH:3]=1.CC1(C)C(C)(C)OB([C:25]2[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:25]2[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=2)[N:5]=[C:4]([N:9]2[CH2:15][CH:14]3[O:16][CH:11]([CH2:12][CH2:13]3)[CH2:10]2)[CH:3]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27735554,4,5,5-Tetramethyl-2-(4-nitrophenyl)-1,3,2-dioxaborolaneHCID 866658833-(6-Chloro-2-iodo-pyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane

Product 1

HCID 866658843-[6-Chloro-2-(4-nitro-phenyl)-pyrimidin-4-yl]-8-oxa-3-aza-bicyclo[3.2.1]octaneYield 79%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

In a 0.5-2 mL microwave vial was placed 3-(6-chloro-2-iodopyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane (16, 50 mg, 0.142 mmol) and 4,4,5,5-tetramethyl-2-(4-nitrophenyl)-1,3,2-dioxaborolane (35.4 mg, 0.142 mmol) in DME (1.5 ml) to give an orange solution. Na2CO3 (2M solution in water) (0.284 ml, 0.569 mmol) was added. The mixture was degassed by bubbling nitrogen through the solution. Pd(PPh3)4 (16.43 mg, 0.014 mmol) was added and the mixture was heated under microwave irradiation for 60 min at 100° C. The mixture was diluted with ethyl acetate and washed with a saturated solution of NaHCO3. The organic phase was dried (MgSO4) and concentrated. The crude product was added to a silica gel column and was eluted with ethyl acetate in hexanes (10-25%). Collected fractions were concentrated to give 39 mg (0.11 mmol, 79%) of the title compound as an off-white/yellow solid. The thus obtained compound was identical to the same compound prepared according to Scheme 5.

Workup

  1. customto give an orange solution
  2. customThe mixture was degassed
  3. customby bubbling nitrogen through the solution
  4. washwashed with a saturated solution of NaHCO3
  5. dry with materialThe organic phase was dried (MgSO4)
  6. concentrationconcentrated
  7. additionThe crude product was added to a silica gel column
  8. washwas eluted with ethyl acetate in hexanes (10-25%)
  9. concentrationCollected fractions were concentrated

Sources & evidence

ORD record
ord-175df4b85986400897600974ae813b32
Source dataset
uspto-grants-2014_09
Patent number
US08835429B2

Linked notes

Loading…