Hydrochloric Acid → HCID 178478967, compound

HRID 2088180Notes

Reaction equation

HRID 2088180 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([CH2:13][O:14][C@@H:15]2[CH2:21][CH2:20][C@@H:19]3[NH:22][C@@:16]2([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:17][C@@H:18]3[C:23]#[CH:24])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C[Si]([N:37]=[N+:38]=[N-:39])(C)C.[ClH:40]>C1(C)C=CC=CC=1.CCOCC>[ClH:40].[F:11][C:9]([F:12])([F:10])[C:7]1[CH:6]=[C:5]([CH2:13][O:14][C@@H:15]2[CH2:21][CH2:20][C@@H:19]3[NH:22][C@@:16]2([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:17][C@H:18]3[C:23]2[NH:39][N:38]=[N:37][CH:24]=2)[CH:4]=[C:3]([C:2]([F:31])([F:1])[F:32])[CH:8]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 78378AzidotrimethylsilaneHCID 86586716HCID 86586716, compound

Product 1

HCID 178478967HCID 178478967, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

(1R*,2R*,5S*,6R*)-2-{[3,5-Bis(trifluoromethyl)phenyl]methoxy}-6-ethynyl-1-phenyl-8-azabicyclo[3.2.1]octane (Example 98; 136 mg, 0.3 mmol) and trimethylsilylazide (0.1 ml, 0.8 mmol) in toluene were heated in a sealed tube at 130° C. for 48 hours. The mixture was allowed to cool and quenched with methanol and water. The mixture was concentrated in vacuo, and the residue purified by flash column chromatography, eluting with 5% methanol/dichloromethane. The debenzylated product was treated with 1.0 eq HCl in ether and the title compound isolated as a white crystalline solid (20 mg, 13%).

Workup

  1. temperatureto cool
  2. customquenched with methanol and water
  3. concentrationThe mixture was concentrated in vacuo
  4. customthe residue purified by flash column chromatography
  5. washeluting with 5% methanol/dichloromethane

Sources & evidence

ORD record
ord-698491a879644e8f8c8bb368229970fb
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

Loading…