tert-Butyl (4-bromonaphthalen-1-yl)carbamate → HCID 68230824, compound

HRID 571110

Reaction equation

HRID 571110 reaction equation
Br[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.C([Li])CCC.[CH:25]([C:27]1[CH:32]=[CH:31][N:30]=[C:29]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH:28]=1)=[O:26]>C1COCC1>[C:15]([O:14][C:13]([NH:12][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([CH:25]([C:27]2[CH:32]=[CH:31][N:30]=[C:29]([NH:33][C:34]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:40])[CH:28]=2)[OH:26])=[CH:3][CH:4]=1)=[O:19])([CH3:18])([CH3:17])[CH3:16]

Participants

5

Reactant 3

HCID 11602218tert-Butyl (4-bromonaphthalen-1-yl)carbamateHCID 21306993tert-Butyl (4-formylpyridin-2-yl)carbamateHCID 178418339Butyllithium

Product 1

HCID 68230824HCID 68230824, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of tert-butyl (4-bromonaphthalen-1-yl)carbamate (WO 2006/010082) (2.09 g, 6.48 mmol) in dry THF (50 mL) under N2 at −78° C. was added n-butyllithium (2.5 M in hexanes, 5.5 mL, 13.8 mmol) over 15 mins. The resulting mixture was maintained at −78° C. for 1.5 hr and then treated with a solution of tert-butyl (4-formylpyridin-2-yl)carbamate (WO 2004/000831) (960 mg, 4.30 mmol) in dry THF (10 mL) in one portion. The reaction mixture was stirred at −78° C. for a further 1 hr and then warmed to RT for 18 hr. The mixture was cooled to 0° C. and the reaction was quenched by the addition of MeOH (5.0 mL), then warmed to RT and partitioned between EtOAc and water. The aq layer was separated and was extracted twice with EtOAc and the combined organic extracts were washed with brine and then dried and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 80 g, EtOAc in isohexane, 0-60%, gradient elution) to afford the title compound, Intermediate F1, as a pale yellow solid (1.13 g, 88% purity (LCMS), 49%); Rt 2.22 min (Method 2); m/z 466 (M+H)+ (ES+). The material so obtained was used in the next step without further purification.

Workup

  1. temperaturewarmed to RT for 18 hr
  2. temperatureThe mixture was cooled to 0° C.
  3. customthe reaction was quenched by the addition of MeOH (5.0 mL)
  4. temperaturewarmed to RT
  5. custompartitioned between EtOAc and water
  6. customThe aq layer was separated
  7. extractionwas extracted twice with EtOAc
  8. washthe combined organic extracts were washed with brine
  9. customdried
  10. customevaporated in vacuo
  11. customThe residue was purified by flash column chromatography (SiO2, 80 g, EtOAc in isohexane, 0-60%, gradient elution)

Sources & evidence

ORD record
ord-c8d00e047b2d4042a42a771bb4946ced
Source dataset
uspto-grants-2015_05
Patent number
US09024041B2

Linked notes

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