Hydrochloric Acid → HCID 86586775, compound

HRID 2088225Notes

Reaction equation

HRID 2088225 reaction equation
[CH2:1]([N:8]1[C@@H:13]2[C@:14]([F:27])([C:16]3[N:20](COCCOC)[N:19]=[N:18][N:17]=3)[CH2:15][C@@:9]1([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C@H:10]([O:28][CH2:29][C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[C:32]([C:40]([F:43])([F:42])[F:41])[CH:31]=1)[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[C:51]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>CCOCC.CO.ClCCl>[CH2:1]([N:8]1[C@@H:13]2[C@:14]([F:27])([C:16]3[N:17]=[N:18][N:19]([CH3:51])[N:20]=3)[CH2:15][C@@:9]1([C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)[C@H:10]([O:28][CH2:29][C:30]1[CH:35]=[C:34]([C:36]([F:38])([F:39])[F:37])[CH:33]=[C:32]([C:40]([F:42])([F:43])[F:41])[CH:31]=1)[CH2:11][CH2:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 86586774HCID 86586774, compound

Product 1

HCID 86586775HCID 86586775, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of (1R*,2R*,5S*,6S*)-8-benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]-methoxy}-6-fluoro-6-[1-(2-methoxyethoxymethyl)-1H-tetrazol-5-yl]-1-phenyl-8-azabicyclo[3.2.1]octane (Example 172; 150 mg, 0.22 mmol), 1M solution of hydrogen chloride in ether (3 ml) and methanol (3 ml) was stirred at reflux for 9 hours. The reaction mixture was concentrated. The residue (170 mg) was treated with dichloromethane (3 ml), methanol (0.5 ml), triphenylphosphine (220 mg, 0.83 mmol) and diethyl azodicarboxylate (0.12 ml, 0.56 mmol). The reaction mixture was stirred at room temperature for 1 hour and concentrated in vacuo to give a 1:3.3 mixture of isomers A and B, respectively. Both isomers were separated by chromatography on silica gel (iso-hexane:ethyl acetate 0-20%).

Workup

  1. temperatureat reflux for 9 hours
  2. concentrationThe reaction mixture was concentrated
  3. stirringThe reaction mixture was stirred at room temperature for 1 hour
  4. concentrationconcentrated in vacuo
  5. customto give
  6. additiona 1:3.3 mixture of isomers A and B
  7. customBoth isomers were separated by chromatography on silica gel (iso-hexane:ethyl acetate 0-20%)

Sources & evidence

ORD record
ord-484a74e257504d56a745df33ad07e0af
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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