Sodium hydride → HCID 86586774, compound

HRID 2088224Notes

Reaction equation

HRID 2088224 reaction equation
[CH2:1]([N:8]1[C@@H:13]2[C@:14]([F:27])([C:16]3[N:20]([CH2:21][O:22][CH2:23][CH2:24][O:25][CH3:26])[N:19]=[N:18][N:17]=3)[CH2:15][C@@:9]1([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C@H:10]([OH:28])[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].C1OCCOCCOCCOCCOCCOC1.[F:55][C:56]([F:70])([F:69])[C:57]1[CH:58]=[C:59]([CH:62]=[C:63]([C:65]([F:68])([F:67])[F:66])[CH:64]=1)[CH2:60]Br>>[CH2:1]([N:8]1[C@@H:13]2[C@:14]([F:27])([C:16]3[N:20]([CH2:21][O:22][CH2:23][CH2:24][O:25][CH3:26])[N:19]=[N:18][N:17]=3)[CH2:15][C@@:9]1([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C@H:10]([O:28][CH2:60][C:59]1[CH:62]=[C:63]([C:65]([F:67])([F:68])[F:66])[CH:64]=[C:57]([C:56]([F:55])([F:69])[F:70])[CH:58]=1)[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 24758Sodium hydrideHCID 2855718-Crown-6HCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 69889711HCID 69889711, compound

Product 1

HCID 86586774HCID 86586774, compoundYield 99.3%

Procedure

(1R*,2R*,5S*,6S*)-8-benzyl-6-fluoro-6-[1-(2-methoxyethoxymethyl)-1H-tetrazol-5-yl]-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol (Description 45; 205 mg, 0.44 mmol) was added to a stirred mixture of sodium hydride (60% in oil, 60 mg, 1.5 mmol, washed twice with iso-hexane) in THF (2 ml) followed by 18-crown-6 (40 mg, 1.5 mmol) and 3,5-bis(trifluoromethyl)benzyl bromide (0.4 ml, 2.16 mmol) at room temperature. The reaction mixture was warm up to reflux and stirred at room temperature overnight, then quenched with saturated aqueous NH4Cl and extracted into diethyl ether. The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica gel (iso-hexane:diethyl ether 10-70%) to give the title compound (303 mg, 97%).

Workup

  1. washwashed twice with iso-hexane) in THF (2 ml)
  2. temperatureThe reaction mixture was warm up
  3. temperatureto reflux
  4. customquenched with saturated aqueous NH4Cl
  5. extractionextracted into diethyl ether
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica gel (iso-hexane:diethyl ether 10-70%)

Sources & evidence

ORD record
ord-3c060cdb48ad4d16abaafc225d32416f
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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