Benzylamine → HCID 58071393, compound

HRID 2178174Notes

Reaction equation

HRID 2178174 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[C:4]([CH3:9])[C:3]=1[O:10][CH3:11].[NH2-].[Na+].[CH2:14]([NH2:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C1COCC1>[CH2:14]([NH:21][C:7]1[CH:2]=[C:3]([O:10][CH3:11])[C:4]([CH3:9])=[C:5]([F:8])[CH:6]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 7504BenzylamineHCID 24533Sodium amideHCID 50998425HCID 50998425, compound

Product 1

HCID 58071393HCID 58071393, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-25 °C

Procedure

To a −78° C. cooled solution of 1-chloro-4-fluoro-2-methoxy-3-methylbenzene (470 mg, 2.69 mmol) in THF (5.5 mL) was added sodium amide (95%, 276 mg, 6.72 mmol). After 30 minutes, the solution was warmed to −20 to −30° C. and then benzylamine (441 μL, 4.05 mmol) was added dropwise over 1 minute. The reaction was stirred overnight, and LCMS showed no starting material. The reaction was quenched by cooling in an ice bath followed by dropwise addition of saturated NH4Cl and water. After stirring for 1 hour, the reaction mix was extracted twice with ethyl acetate, and the combined organic phases dried over MgSO4 and concentrated via rotary evaporation. The crude product was purified by silica gel chromatography (0-30% ethyl acetate/hexanes) to yield a 223 mg (34%) of N-benzyl-3-fluoro-5-methoxy-4-methylaniline as an orange oil. 1H NMR (300 MHz, CDCl3) δ 7.40-7.27 (m, 5H), 6.06-6.00 (m, 1H), 6.00 (s, 1H), 4.29 (s, 2H), 3.74 (s, 3H), 2.00 (s, 3H); LCMS (m/z): 246 (MH+).

Workup

  1. customThe reaction was quenched
  2. temperatureby cooling in an ice bath
  3. additionfollowed by dropwise addition of saturated NH4Cl and water
  4. stirringAfter stirring for 1 hour
  5. additionthe reaction mix
  6. extractionwas extracted twice with ethyl acetate
  7. dry with materialthe combined organic phases dried over MgSO4
  8. concentrationconcentrated via rotary evaporation
  9. customThe crude product was purified by silica gel chromatography (0-30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-31d2473ee167478f9528437b1da6eb7d
Source dataset
uspto-grants-2015_06
Patent number
US09067925B2

Reaction notes

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