Acetic Acid → HCID 10046876, compound

HRID 392155Notes

Reaction equation

HRID 392155 reaction equation
[O:1]1[C:6]2=[C:7]3[C:12](=[CH:13][CH:14]=[C:5]2[O:4][CH2:3][C@@H:2]1[CH2:15][NH:16][CH2:17][CH2:18][CH2:19][C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([F:29])[CH:27]=2)[NH:22][CH:21]=1)[N:11]=[CH:10][CH:9]=[CH:8]3.C=O.[C:32]([BH3-])#N.[Na+].C(O)(=O)C>CO>[O:1]1[C:6]2=[C:7]3[C:12](=[CH:13][CH:14]=[C:5]2[O:4][CH2:3][CH:2]1[CH2:15][N:16]([CH2:17][CH2:18][CH2:19][C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([F:29])[CH:27]=2)[NH:22][CH:21]=1)[CH3:32])[N:11]=[CH:10][CH:9]=[CH:8]3

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 23521565HCID 23521565, compound

Product 1

HCID 10046876HCID 10046876, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (2S)-(2,3-dihydro-[1,4]dioxino[2,3-f]quinolin-2-ylmethyl)-[3-(5-fluoro-1H-indol-3-yl)-propyl]-amine (0.13 g, 0.33 mmol) and formaldehyde (37 wt. % in water, 0.26 g, 3.3 mmol) in methanol (20 mL) was added sodium cyanoborohydride (0.038 g, 0.59 mmol) and acetic acid (0.03 g, 0.5 mmol) at room temperature. The mixture was stirred at room temperature under nitrogen overnight, then quenched with 1N NaOH (5 mL). The mixture was extracted with methylene chloride (3×50 mL). The organic layer was washed with water (3×50 mL), dried over anhydrous sodium sulfate, filtered and the solvent was removed under vacuum. The crude oil was column chromatographed on silica gel (5% methanol-methylene chloride). The product-containing fractions were concentrated in vacuum to give 0.1 g of the (S)-enantiomer of the title compound as a brown oil. The dihydrochloride salt was prepared in ethyl acetate as a yellow solid (decomposed at 78° C.).

Workup

  1. customquenched with 1N NaOH (5 mL)
  2. extractionThe mixture was extracted with methylene chloride (3×50 mL)
  3. washThe organic layer was washed with water (3×50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed under vacuum
  7. customchromatographed on silica gel (5% methanol-methylene chloride)
  8. concentrationThe product-containing fractions were concentrated in vacuum

Sources & evidence

ORD record
ord-34ce47c6eac847c18fb8bc79425b384f
Source dataset
uspto-grants-2004_10
Patent number
US06800637B2

Reaction notes

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