Acetic Acid → HCID 10477388, compound

HRID 392162Notes

Reaction equation

HRID 392162 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][CH2:13][NH:14][CH2:15][CH:16]1[O:25][C:24]2[C:19](=[CH:20][CH:21]=[C:22]3[N:28]=[C:27]([CH3:29])[O:26][C:23]3=2)[O:18][CH2:17]1.[CH:30](=O)[CH3:31].C([BH3-])#N.[Na+].C(O)(=O)C>CO>[CH2:30]([N:14]([CH2:13][CH2:12][CH2:11][C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=2)[NH:7][CH:6]=1)[CH2:15][CH:16]1[CH2:17][O:18][C:19]2[CH:20]=[CH:21][C:22]3[N:28]=[C:27]([CH3:29])[O:26][C:23]=3[C:24]=2[O:25]1)[CH3:31]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 177AcetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 10340653HCID 10340653, compound

Product 1

HCID 10477388HCID 10477388, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of [3-(5-fluoro-1H-indol-3-yl)-propyl]-(2-methyl-7,8-dihydro-1,6,9trioxa-3-aza-cyclopenta[a]napthalen-8-ylmethyl)-amine (0.13 g, 0.32 mmol) and acetaldehyde (0.18 mL, 3.2 mmol) in methanol (20 mL) was added sodium cyanoborohydride (0.07 g, 0.57 mmol) and acetic acid (0.04 mL, 0.32 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 145 mg of the (S)-enantiomer of the title compound as a yellow oil. The dihydrochloride salt was prepared in ethyl acetate as a white solid, m.p. 115° C. d.

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-d35e465ff8744cf596411423ccd69aa7
Source dataset
uspto-grants-2004_10
Patent number
US06800637B2

Reaction notes

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