2,4-Dichloropyrimidine → tert-Butyl 4-(2-chloropyrimidin-4-yloxy)naphthalen-1-ylcarbamate

HRID 2069149Notes

Reaction equation

HRID 2069149 reaction equation
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=1.C1CCN2C(=NCCC2)CC1.[Cl:31][C:32]1[N:37]=[C:36](Cl)[CH:35]=[CH:34][N:33]=1>CC#N>[Cl:31][C:32]1[N:37]=[C:36]([O:1][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[CH:4][CH:3]=2)[CH:35]=[CH:34][N:33]=1

Participants

5

Reactant 3

HCID 775312,4-DichloropyrimidineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 10923237tert-Butyl (4-hydroxynaphthalen-1-yl)carbamate

Product 1

HCID 86660490tert-Butyl 4-(2-chloropyrimidin-4-yloxy)naphthalen-1-ylcarbamateYield 35.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a degassed solution of tert-butyl 4-hydroxynaphthalen-1-ylcarbamate (13.3 g, 51.3 mmol) and DBU (12.6 mL, 51.3 mmol) in MeCN (80 mL) under nitrogen was added 2,4-dichloropyrimidine (7.65 g, 51.3 mmol) in acetonitrile (19 mL) and the reaction mixture was heated to reflux for 4 hr. The solvent was evaporated in vacuo and the residue was taken up into DCM (100 mL) and was washed with water (2×100 mL) and brine (100 mL), then dried (MgSO4) and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 330 g, EtOAc in isohexane, 0-50%, gradient elution) to afford the title compound as a pale pink solid (6.80 g, 34%); Rt 2.50 min (Method 2); m/z 372/374 (M+H)+, (ES+)+.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 4 hr
  3. customThe solvent was evaporated in vacuo
  4. washwas washed with water (2×100 mL) and brine (100 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated in vacuo
  7. customThe residue was purified by flash column chromatography (SiO2, 330 g, EtOAc in isohexane, 0-50%, gradient elution)

Sources & evidence

ORD record
ord-7449f2539e8440288049f9602ea94c3b
Source dataset
uspto-grants-2012_10
Patent number
US08299074B2

Reaction notes

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