Acetic Acid → (6R,9R)-6-(2,3-difluorophenyl)-3-(dimethylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol

HRID 1666147Notes

Reaction equation

HRID 1666147 reaction equation
[C:1]([BH3-])#[N:2].[Na+].N[C:6]1[CH:7]=[C:8]2[CH2:16][C@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=3[F:24])[CH2:14][CH2:13][C@@H:12]([OH:25])[C:9]2=[N:10][CH:11]=1.C=O.[C:28](O)(=O)C>C(#N)C>[F:24][C:18]1[C:19]([F:23])=[CH:20][CH:21]=[CH:22][C:17]=1[C@@H:15]1[CH2:14][CH2:13][C@@H:12]([OH:25])[C:9]2=[N:10][CH:11]=[C:6]([N:2]([CH3:1])[CH3:28])[CH:7]=[C:8]2[CH2:16]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 57911417(6R,9R)-3-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol

Product 1

HCID 57911469(6R,9R)-6-(2,3-difluorophenyl)-3-(dimethylamino)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-olYield 45%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

SODIUM CYANOBOROHYDRIDE (242 mg, 3.86 mmol) was added to the Acetonitrile (2 mL) solution of (6R,9R)-3-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol (56 mg, 0.193 mmol) and FORMALDEHYDE (1 mL, 13.43 mmol) at rt. The reaction was stirred at room temperature for 4 hours. ACETIC ACID (0.5 mL, 8.73 mmol) was added to the reaction mixture (Caution: heat generation was observed to cause acetonitrile reflux) and the reaction was stirred overnight. Volatile was removed mostly via vacuum and the crude was added NaOH (1N), extracted with ethyl acetate twice. The ethyl acetate layer was dried (Na2SO4), filtered and concentrated. Flash column by methanol in CH2Cl2 from 0 to 4% gave the desired product (27.6 mg, 45%). MS(ESI)[M+H+]=319.35.

Workup

  1. stirringthe reaction was stirred overnight
  2. customVolatile was removed mostly via vacuum
  3. additionthe crude was added NaOH (1N)
  4. extractionextracted with ethyl acetate twice
  5. dry with materialThe ethyl acetate layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-2fcf233feb8c4ac38af882f8c19a9f9d
Source dataset
uspto-grants-2011_10
Patent number
US08044043B2

Reaction notes

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