Tryptophol → HCID 44238076, compound

HRID 2066964Notes

Reaction equation

HRID 2066964 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:35])(=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][C:18]([F:35])=[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 44238076HCID 44238076, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The more polar 4-dimethylamino-2-fluoro-4-phenylcyclohexanone (950 mg, 4.04 mmol) together with tryptophol (723 mg, 4.04 mmol) was dissolved in absolute dichloromethane (45 ml) at 0° C. (inside temperature). Trimethylsilyl triflate (987 mg, 4.44 mmol, 0.81 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 (60 ml) was added to the reaction mixture and stirred for 10 min. A colourless solid separated out of the two-phase mixture. This was filtered off by means of a fritted glass filter and then washed with methanol (50 ml). The solid was the more polar diastereoisomer (241 mg). The more polar diastereoisomer was separated from the filtrate again and filtered off once again. After phase separation the aqueous phase was extracted with dichloromethane (4×40 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 19:1 (1000 ml), methanol (500 ml)]. 676 mg (1.70 mmol, 42%, mp 260-265° C.) of a more non-polar diastereomer and a total of 572 mg (1.44 mmol, 36%, mp 237-242° C.) of the more polar diastereoisomer were isolated.

Workup

  1. stirringstirred for 10 min
  2. customA colourless solid separated out of the two-phase mixture
  3. filtrationThis was filtered off by means of a fritted glass
  4. filtrationfilter
  5. washwashed with methanol (50 ml)
  6. customThe more polar diastereoisomer was separated from the filtrate again
  7. filtrationfiltered off once again
  8. customAfter phase separation the aqueous phase
  9. extractionwas extracted with dichloromethane (4×40 ml)
  10. dry with materialThe combined organic phases were dried over sodium sulphate
  11. filtrationfiltered
  12. customto separate the residue by chromatography [silica gel (150 g), chloroform/ethanol 19:1 (1000 ml), methanol (500 ml)]
  13. custom676 mg (1.70 mmol, 42%, mp 260-265° C.) of a more non-polar diastereomer and a total of 572 mg (1.44 mmol, 36%, mp 237-242° C.) of the more polar diastereoisomer were isolated

Sources & evidence

ORD record
ord-f7f7453af85045f8b7095e2c14ade642
Source dataset
uspto-grants-2012_10
Patent number
US08293758B2

Reaction notes

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