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

HRID 1738319Notes

Reaction equation

HRID 1738319 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 were taken into a 2M solution of NH3 and then extracted thrice with diethyl ether. The combined ether portions were dried (MgSO4), filtered, and the solvent 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. extractionextracted thrice with diethyl ether
  5. dry with materialThe combined ether portions were dried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent removed in vacuo
  8. customto give the crude residue

Sources & evidence

ORD record
ord-562b0044ce9f48bca840c78f51e09d31
Source dataset
uspto-grants-1999_10
Patent number
US05962514

Reaction notes

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