Hydrochloric Acid → HCID 10163084, compound

HRID 1267904Notes

Reaction equation

HRID 1267904 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.[CH:16]1([O:19][C:20]2[CH:27]=[CH:26][C:25]([N:28]3[C:32]([C:33]([F:36])([F:35])[F:34])=[N:31][N:30]=[N:29]3)=[CH:24][C:21]=2[CH:22]=O)[CH2:18][CH2:17]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCCl.C(OCC)(=O)C.C(O)(=O)C>[CH:16]1([O:19][C:20]2[CH:27]=[CH:26][C:25]([N:28]3[C:32]([C:33]([F:34])([F:35])[F:36])=[N:31][N:30]=[N:29]3)=[CH:24][C:21]=2[CH2:22][NH:1][C@@H:2]2[CH2:8][CH2:7][C@@H:6]3[NH:9][C@@:3]2([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:4][CH2:5]3)[CH2:18][CH2:17]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 5049666Sodium triacetoxyborohydrideHCID 10902590HCID 10902590, compoundHCID 69654642HCID 69654642, compound

Product 1

HCID 10163084HCID 10163084, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

(1R*,2R*,5S*)-2-Amino-1-phenyl-8-azabicyclo[3.2.1]octane (Description 6; 50 mg, 0.25 mmol) and 2-(cyclopropoxy)-5-[5-(trifluoromethyl)tetrazol-1-yl]benzaldehyde (119 mg, 0.4 mmol) [See International (PCT) Patent Publication No. WO 99/24423, published 20 May 1999] were dissolved in 1,2-dichloroethane (5 mL) and treated with acetic acid (23 μL), followed by sodium triacetoxyborohydride (85 mg). The solution was stirred at ambient temperature for 16 hours, then quenched with saturated aqueous sodium hydrogen carbonate solution (50 mL). The mixture was extracted with dichloromethane (2×50 mL) and the extracts were dried (MgSO4), then concentrated. The residue was purified by silica chromatography to give the free base, which was taken up in ethyl acetate (10 mL) and treated with ethereal hydrogen chloride (1M, 2 mL). The solid formed was removed by filtration and recrystallized from methanol/ethyl acetate to give the title compound as a white solid (84 mg, 0.15 mmol).

Workup

  1. customquenched with saturated aqueous sodium hydrogen carbonate solution (50 mL)
  2. extractionThe mixture was extracted with dichloromethane (2×50 mL)
  3. dry with materialthe extracts were dried (MgSO4)
  4. concentrationconcentrated
  5. customThe residue was purified by silica chromatography
  6. customto give the free base, which
  7. customThe solid formed
  8. customwas removed by filtration
  9. customrecrystallized from methanol/ethyl acetate

Sources & evidence

ORD record
ord-9fb4a5d1b2ae4b5bb43c7cd9e1828038
Source dataset
uspto-grants-2003_04
Patent number
US06555552B2

Reaction notes

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