Tryptophol → HCID 44237878, compound

HRID 2066963Notes

Reaction equation

HRID 2066963 reaction equation
[CH3:1][N:2]([CH3:17])[C:3]1([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:8][CH2:7][C:6](=[O:9])[CH:5]([F:10])[CH2:4]1.[CH:18]1[CH:19]=[CH:20][C:21]2[NH:26][CH:25]=[C:24]([CH2:27][CH2:28]O)[C:22]=2[CH:23]=1.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.[OH-].[Na+]>ClCCl>[F:10][CH:5]1[C:6]2([C:25]3[NH:26][C:21]4[C:22]([C:24]=3[CH2:27][CH2:28][O:9]2)=[CH:23][CH:18]=[CH:19][CH:20]=4)[CH2:7][CH2:8][C:3]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)([N:2]([CH3:17])[CH3:1])[CH2:4]1

Participants

6

Reactant 4

HCID 10685TryptopholHCID 14798Sodium HydroxideHCID 65367Trimethylsilyl triflateHCID 67408514HCID 67408514, compound

Product 1

HCID 44237878HCID 44237878, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(±)-4-dimethylamino-2-fluoro-4-phenylcyclohexanone (1.61 g, 6.83 mmol, mixture of both diastereoisomers, mainly polar diastereoisomer) together with tryptophol (1.10 g, 6.83 mmol) was dissolved in absolute dichloromethane (75 ml) at 0° C. (inside temperature). Trimethylsilyl triflate (1.67 g, 7.51 mmol, 1.36 ml, 1.225 g/ml) was then added quickly in drops to absolute dichloromethane (10 ml). The reaction mixture immediately changed colour from yellow to red-brown. The reaction mixture was stirred for 5 h at room temperature and became cloudy during this. 5N sodium hydroxide solution (100 ml) was added to the reaction mixture and stirred for 10 min. After phase separation the aqueous phase was extracted with dichloromethane (4×50 ml). The combined organic phases were dried over sodium sulphate, filtered and then completely freed of volatile constituents in a vacuum. An attempt was made to separate the residue by chromatography [silica gel (150 g), chloroform/ethanol 50:1 (500 ml), 19:1 (500 ml), 9:1 (1000 ml), 1:1 (500 ml), methanol (1000 ml)]. 467 mg (1.23 mmol, 18%, mp 259-263° C.) of a more non-polar diastereomer, 506 mg (1.34 mmol, 20%, mp 217-222° C.) of a diastereomer of average polarity and 168 mg (0.44 mmol, 6%, mp 245-247° C.) of a more polar diastereoisomer were isolated. The individual fractions were recrystallised from methanol.

Workup

  1. stirringstirred for 10 min
  2. customAfter phase separation the aqueous phase
  3. extractionwas extracted with dichloromethane (4×50 ml)
  4. dry with materialThe combined organic phases were dried over sodium sulphate
  5. filtrationfiltered
  6. customto separate the residue by chromatography [silica gel (150 g), chloroform/ethanol 50:1 (500 ml), 19:1 (500 ml), 9:1 (1000 ml), 1:1 (500 ml), methanol (1000 ml)]
  7. custom467 mg (1.23 mmol, 18%, mp 259-263° C.) of a more non-polar diastereomer, 506 mg (1.34 mmol, 20%, mp 217-222° C.) of a diastereomer of average polarity and 168 mg (0.44 mmol, 6%, mp 245-247° C.) of a more polar diastereoisomer were isolated
  8. customThe individual fractions were recrystallised from methanol

Sources & evidence

ORD record
ord-c1841fd5b62c4cb481a8ce7a4178c8f7
Source dataset
uspto-grants-2012_10
Patent number
US08293758B2

Reaction notes

Loading…