Trifluoroacetic acid → (4R,9aR)-6-(1-(S)-Hydroxy-ethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene

HRID 11947Notes

Reaction equation

HRID 11947 reaction equation
C(OC([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([CH:22]([OH:24])[CH3:23])=[CH:14][CH:13]=3)[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[OH:24][C@H:22]([C:15]1[N:16]=[C:17]2[C:12](=[CH:13][CH:14]=1)[CH2:11][C@H:10]1[N:18]2[C@H:19]([CH3:21])[CH2:20][NH:8][CH2:9]1)[CH3:23]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67237860(4R,9aR)-6-(1-(RS)-Hydroxy-ethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

Product 1

HCID 21044398(4R,9aR)-6-(1-(S)-Hydroxy-ethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3.09 g (9.27 mmol) (4R,9aR)-6-(1-(RS)-hydroxy-ethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (Example 38, intermediate) in 33 ml dichloromethane was cooled to 0 deg C. and treated with 8.8 ml (12.7 g, 0.11 mol) trifluoroacetic acid. The cooling bath was removed and the volatile components were removed on a rotary evaporator. The residue was chromatographed on silica gel (0.032–0.063 mm) with dichloromethane:methanol:ammonia (19:1:0.1). The remaining oil was dissolved in dichloromethane and saturated aqueous sodium bicarbonate solution and extracted until all product was extracted from the aqueous phase. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The remaining light brown oil was chromatographed on a Chiralpak-AD column with 7% ethanol/n-heptane yielding the two diastereomers, the R-diastereomer being eluted first.

Workup

  1. customThe cooling bath was removed
  2. customthe volatile components were removed on a rotary evaporator
  3. customThe residue was chromatographed on silica gel (0.032–0.063 mm) with dichloromethane:methanol:ammonia (19:1:0.1)
  4. dissolutionThe remaining oil was dissolved in dichloromethane
  5. extractionsaturated aqueous sodium bicarbonate solution and extracted until all product
  6. extractionwas extracted from the aqueous phase
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customThe remaining light brown oil was chromatographed on a Chiralpak-AD column with 7% ethanol/n-heptane yielding the two diastereomers
  12. washthe R-diastereomer being eluted first

Sources & evidence

ORD record
ord-391941e392754a1e9238011a72cda5be
Source dataset
uspto-grants-2006_08
Patent number
US07098337B2

Reaction notes

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