Sodium Bicarbonate → HCID 86586085, compound

HRID 1267906Notes

Reaction equation

HRID 1267906 reaction equation
[NH2:1][C@@H:2]1[CH2:8][CH2:7][C@@H:6]2[NH:9][C@@:3]1([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH2:4][CH2:5]2.[Cl:16][C:17]1[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:28])[F:27])=[CH:21][C:18]=1[CH:19]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>ClCCCl.C(O)(=O)C.CO>[ClH:16].[ClH:16].[Cl:16][C:17]1[CH:24]=[CH:23][C:22]([O:25][C:26]([F:27])([F:28])[F:29])=[CH:21][C:18]=1[CH2:19][NH:1][C@@H:2]1[CH2:8][CH2:7][C@@H:6]2[NH:9][C@@:3]1([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH2:4][CH2:5]2

Participants

9

Reactant 5

HCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 185425172-Chloro-5-(trifluoromethoxy)benzaldehydeHCID 69654642HCID 69654642, compound

Product 1

HCID 86586085HCID 86586085, compoundYield 56.6%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

(1R*,2R*,5S*)-2-Amino-1-phenyl-8-azabicyclo[3.2.1]octane (Description 6; 77 mg, 0.38 mmol) and 2-chloro-5-(trifluoromethoxy)benzaldehyde (Description 27; 120 mg, 0.53 mmol) were dissolved in 1,2-dichloroethane (5 mL) and acetic acid (1mL), then treated with sodium triacetoxyborohydride (128 mg, 0.6 mmol). The suspension was stirred at room temperature for 16 hours, then diluted with methanol (5 mL). Sodium cyanoborohydride was added (200 mg, 0.9 mmol) and this solution stirred for a further 16 hours at ambient temperature. The resulting mixture was poured into saturated aqueous sodium hydrogen carbonate solution (50 mL) and extracted with dichloromethane (2×50 mL). The extracts were dried (MgSO4) and concentrated to yield a gum, which was purified by silica chromatography. The pure free base was dissolved in ethyl acetate (10 mL) and treated with ethereal hydrogen chloride (2 mL, 1M). The solid formed was removed by filtration, washed with diethyl ether and dried to give the title compound as a solid (46 mg, 0.1 mmol).

Workup

  1. stirringthis solution stirred for a further 16 hours at ambient temperature
  2. extractionextracted with dichloromethane (2×50 mL)
  3. dry with materialThe extracts were dried (MgSO4)
  4. concentrationconcentrated
  5. customto yield a gum, which
  6. customwas purified by silica chromatography
  7. dissolutionThe pure free base was dissolved in ethyl acetate (10 mL)
  8. additiontreated with ethereal hydrogen chloride (2 mL, 1M)
  9. customThe solid formed
  10. customwas removed by filtration
  11. washwashed with diethyl ether
  12. customdried

Sources & evidence

ORD record
ord-fc074bf01e0c48cca930e4cd78220d94
Source dataset
uspto-grants-2003_04
Patent number
US06555552B2

Reaction notes

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