Sodium Carbonate → 3-Hexyl-6-(3-hydroxyphenyl)-6-methyl-3-azabicyclo[3.1.0]hexan-2-one

HRID 428958Notes

Reaction equation

HRID 428958 reaction equation
N[C:2]1[CH:3]=[C:4]([C:8]2([CH3:21])[CH:13]3[CH:9]2[CH2:10][N:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:12]3=[O:14])[CH:5]=[CH:6][CH:7]=1.N([O-])=[O:23].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>Cl.O>[CH2:15]([N:11]1[CH2:10][CH:9]2[CH:13]([C:8]2([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([OH:23])[CH:3]=2)[CH3:21])[C:12]1=[O:14])[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 221411996-(3-Aminophenyl)-3-hexyl-6-methyl-3-azabicyclo[3.1.0]hexan-2-oneHCID 23668193Sodium Nitrite

Product 1

HCID 221411943-Hexyl-6-(3-hydroxyphenyl)-6-methyl-3-azabicyclo[3.1.0]hexan-2-oneYield 34%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent2×

Conditions

Temperature
0 °C

Procedure

6-(3-Aminophenyl)-3-hexyl-6-methyl-3-azabicyclo[3.1.0]hexan-2-one (Preparation 84, 1.0 g, 3.5 mmol) was dissolved in aqueous hydrochloric acid (2.5 M, 3.5 ml) and cooled to 0° C. Sodium nitrite (0.25 g, 3.6 mmol) dissolved in water (I ml) was added to the reaction mixture and stirred for 30 min. The reaction mixture was neutralised with solid sodium carbonate and then diluted with water (5 ml). The reaction mixture was heated to 60° C. for 1 h during which time a dark brown oil formed on top of the aqueous layer. The product was extracted with dichloromethane (50 ml), and the organic extracts were dried (Na2SO4) and concentrated in vacuo to give a brown oil. The crude product was purified by chromatography on silica gel (20 g) eluting with ethyl acetate:hexane (1:1) to give the title compound (0.34 g, 34%).

Workup

  1. additionwas added to the reaction mixture
  2. temperatureThe reaction mixture was heated to 60° C. for 1 h during which time a dark brown oil
  3. customformed on top of the aqueous layer
  4. extractionThe product was extracted with dichloromethane (50 ml)
  5. dry with materialthe organic extracts were dried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customto give a brown oil
  8. customThe crude product was purified by chromatography on silica gel (20 g)
  9. washeluting with ethyl acetate:hexane (1:1)

Sources & evidence

ORD record
ord-f18c4693098d4a0b85f0641c8fd8d916
Source dataset
uspto-grants-2001_11
Patent number
US06313312B1

Reaction notes

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