Acetic Acid → (R)-3-(N-Cyclobutyl-N-n-propylamino)-8-fluoro-5-methoxy-3,4-dihydro-2H-1-benzopyran

HRID 52272Notes

Reaction equation

HRID 52272 reaction equation
[CH:1]1([NH:5][C@@H:6]2[CH2:11][C:10]3[C:12]([O:17][CH3:18])=[CH:13][CH:14]=[C:15]([F:16])[C:9]=3[O:8][CH2:7]2)[CH2:4][CH2:3][CH2:2]1.[CH3:19][CH2:20][CH:21]=O.C([BH3-])#N.[Na+].C(O)(=O)C>CO>[CH:1]1([N:5]([C@@H:6]2[CH2:11][C:10]3[C:12]([O:17][CH3:18])=[CH:13][CH:14]=[C:15]([F:16])[C:9]=3[O:8][CH2:7]2)[CH2:19][CH2:20][CH3:21])[CH2:2][CH2:3][CH2:4]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 527PropanalHCID 5003444Sodium cyanoborohydrideHCID 53650127HCID 53650127, compound

Product 1

HCID 22871218(R)-3-(N-Cyclobutyl-N-n-propylamino)-8-fluoro-5-methoxy-3,4-dihydro-2H-1-benzopyranYield 80.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(R)-3-(N-Cyclobutylamino)-8-fluoro-5-methoxy-3,4-dihydro-2H-1-benzopyran (1.01 g, 4.02 mmol) was dissolved in anhydrous methanol (20 mL) and to this was n-propionaldehyde (3.0 mL, 40.2 mmol) added. After 1 h the reaction was cooled (ice-bath) then sodium cyanoborohydride (0.46 g, 7.24 mmol) was added, the pH was adjusted to 4-5 with acetic acid and the reaction was allowed to stir at room temperature over the weekend. The solvent was removed in vacuo, the remains extracted thrice with diethyl ether. The combined ether portions were dried (MgSO4) filtered, and the solvent were taken into a 2M solution of NH3 and then removed in vacuo to give the crude residue. Chromatography on silica (eluent: 11% ethyl acetate/hexane) gave 0.95 g (80% yield) of the title compound as a clear oil. [α]21D =-95.4° (C=0.1; CHCl3) GC-MS (70 eV) M=293 (1%).

Workup

  1. additionadded
  2. temperatureAfter 1 h the reaction was cooled (ice-bath)
  3. customThe solvent was removed in vacuo
  4. extractionthe remains extracted thrice with diethyl ether
  5. dry with materialThe combined ether portions were dried (MgSO4)
  6. filtrationfiltered
  7. customremoved in vacuo
  8. customto give the crude residue

Sources & evidence

ORD record
ord-52880a17bb9b4f3d90dd1edb0f188ee1
Source dataset
uspto-grants-1997_04
Patent number
US05616610

Reaction notes

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