Triphenylphosphine → (1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy)-6-{2-[2-(t-butoxycarbonylamino)ethyl]-2H-tetrazol-5-yl}-1-phenyl-8-azabicyclo[3.2.1]octane

HRID 2088204Notes

Reaction equation

HRID 2088204 reaction equation
CCOC(/N=N/C(OCC)=O)=O.[CH2:13]([N:20]1[C@@H:25]2[C@H:26]([C:28]3[NH:32][N:31]=[N:30][N:29]=3)[CH2:27][C@@:21]1([C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)[C@H:22]([O:33][CH2:34][C:35]1[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[C:37]([C:45]([F:48])([F:47])[F:46])[CH:36]=1)[CH2:23][CH2:24]2)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[C:55]([O:59][C:60]([NH:62][CH2:63][CH2:64]O)=[O:61])([CH3:58])([CH3:57])[CH3:56].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[CH2:13]([N:20]1[C@@H:25]2[C@H:26]([C:28]3[N:32]=[N:31][N:30]([CH2:64][CH2:63][NH:62][C:60]([O:59][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:61])[N:29]=3)[CH2:27][C@@:21]1([C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)[C@H:22]([O:33][CH2:34][C:35]1[CH:36]=[C:37]([C:45]([F:48])([F:47])[F:46])[CH:38]=[C:39]([C:41]([F:42])([F:43])[F:44])[CH:40]=1)[CH2:23][CH2:24]2)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 2733206tert-butyl N-(2-hydroxyethyl)carbamateHCID 5462977Diethyl azodicarboxylateHCID 178506223HCID 178506223, compound

Product 1

HCID 86586752(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy)-6-{2-[2-(t-butoxycarbonylamino)ethyl]-2H-tetrazol-5-yl}-1-phenyl-8-azabicyclo[3.2.1]octaneYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethylazodicarboxylate, 0.15 g, 0.86 mmol was added to a solution of (1R*,2 R*,5S*,6R*)-8-benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxyl 1-phenyl-6-(tetrazol-5-yl)-8-azabicyclo[3.2.1]octane (Example 138; 0.5 g, 0.85 mmol), [N-(t-butoxy-carbonyl)ethanolamine] (0.15 g, 0.93 mmol) and triphenylphosphine (0.23 g, 0.88 mmol) in dichloromethane (20 ml). The mixture was stirred at room temperature for 2 hours then concentrated in vacuo. The residue was chromatographed on silica gel eluting with 10, 20 and 30% ethyl acetate/iso-hexanes to yield the title compound (543 mg, 88%).

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe residue was chromatographed on silica gel eluting with 10, 20 and 30% ethyl acetate/iso-hexanes

Sources & evidence

ORD record
ord-8d16eac6b904471991e4cd11425c444b
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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