Methanol → (R)-8-Fluoro-5-methoxycarbonyl-3-(N-3-pentyl-N-n-propylamino)chroman

HRID 37676Notes

Reaction equation

HRID 37676 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5](OS(C(F)(F)F)(=O)=O)=[C:6]2[C:11]=1[O:10][CH2:9][C@H:8]([N:12]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[CH2:13][CH2:14][CH3:15])[CH2:7]2.C1(P(C2C=CC=CC=2)CC(P(C2C=CC=CC=2)C2C=CC=CC=2)C)C=CC=CC=1.C(N(CC)CC)C.[CH3:65][OH:66].CN([CH:70]=[O:71])C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:65]([O:71][CH3:70])=[O:66])=[C:6]2[C:11]=1[O:10][CH2:9][C@H:8]([N:12]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[CH2:13][CH2:14][CH3:15])[CH2:7]2

Participants

7

Reactant 5

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 36406851,2-Bis(diphenylphosphino)propaneHCID 54407297(R)-8-fluoro-3-(N-3-pentyl-N-n-propylamino)-5-trifluoromethanesulfonyloxychroman

Product 1

HCID 53912065(R)-8-Fluoro-5-methoxycarbonyl-3-(N-3-pentyl-N-n-propylamino)chroman

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

(R)-8-Fluoro-3-(N-3-pentyl-N-n-propylamino)-5-trifluoromethanesulfonyloxychroman (1.04 g, 2.43 mmol), palladium(II)acetate (55 mg), 1,2-bis(diphenylphosphino)propane (100 mg) was dissolved in 10 ml DMF. Triethylamine (0.75 ml, 5.38 mmol) and MeOH (1.0 ml, 24.6 mmol) was added under CO atm. via septa. The solution was stirred at +70° C. for 18 hours, and thereafter evaporated to dryness. 100 ml 2M NH3 and 100 ml EtOAc was added and the aqueous phase was extracted with 100 ml EtOAc. The combined organic layers was dried (MgSO4) and evaporated. Flash chromatography on silica with a gradient of Hexane-Hexane:EtOAc, 50:1 gave 0.76 g of (R)-8-fluoro-5-methyloxycarbonyl-3-(N-3-pentyl-N-n-propylamino)chroman as an uncoloured oil. Purity: 94% according to GC.

Workup

  1. customevaporated to dryness
  2. addition100 ml 2M NH3 and 100 ml EtOAc was added
  3. extractionthe aqueous phase was extracted with 100 ml EtOAc
  4. dry with materialThe combined organic layers was dried (MgSO4)
  5. customevaporated

Sources & evidence

ORD record
ord-2f10b16ca6f94b7eac21905406da0493
Source dataset
uspto-grants-1995_05
Patent number
US05420151

Reaction notes

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