Hydrochloric Acid → (R)-2-(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-ylamino) ethanol

HRID 1807614Notes

Reaction equation

HRID 1807614 reaction equation
[Si]([O:8][CH2:9][CH2:10][N:11]([C@H:19]1[C:27]2[C:22](=[C:23]([C:28]3[N:32]=[C:31]([C:33]4[S:34][C:35]([C:44]([F:47])([F:46])[F:45])=[C:36]([C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)[CH:37]=4)[O:30][N:29]=3)[CH:24]=[CH:25][CH:26]=2)[CH2:21][CH2:20]1)C(=O)OC(C)(C)C)(C(C)(C)C)(C)C.Cl.CCOCC>C(Cl)Cl>[C:38]1([C:36]2[CH:37]=[C:33]([C:31]3[O:30][N:29]=[C:28]([C:23]4[CH:24]=[CH:25][CH:26]=[C:27]5[C:22]=4[CH2:21][CH2:20][C@H:19]5[NH:11][CH2:10][CH2:9][OH:8])[N:32]=3)[S:34][C:35]=2[C:44]([F:46])([F:47])[F:45])[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 67197415(R)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)carbamate

Product 1

HCID 67319515(R)-2-(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-ylamino) ethanolYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)carbamate INT-63 (0.108 g, 0.16 mmol) dissolved in DCM (1.5 mL) was added 2N HCl in ether (1.45 mL, 2.9 mmol). The solution was stirred at room temperature for 12 h. The solvent was removed under a stream of nitrogen and the product dried under vacuum to afford 0.052 g (65%) of (R)-2-(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-ylamino)ethanol 67 as the HCl salt. LCMS-ESI (m/z): calcd for C24H20F3N3O2S: 471.5; found 472.1 [M+H]+, tR=7.43 min (Method 2). 1H NMR (400 MHz, CDCl3) δ 9.62 (s, 1H), 8.19 (d, J=7.6, 1H), 8.03 (d, J=7.5, 1H), 7.87 (t, J=1.5, 1H), 7.53-7.40 (m, 6H), 4.86 (d, J=4.8, 1H), 3.88 (s, 2H), 3.74-3.50 (m, 1H), 3.41 (ddd, J=13.3, 9.4, 4.4, 1H), 3.06 (m, 1H), 2.98 (m, 1H), 2.67-2.42 (m, 2H). 13C NMR (100 MHz, DMSO) δ 169.22, 168.07, 145.68, 144.75, 139.39, 135.43, 132.42, 129.42, 129.37, 129.25, 128.69, 128.27, 127.62, 126.41, 123.16, 122.37, 120.47, 61.10, 56.63, 46.54; 31.66, 27.80.

Workup

  1. customThe solvent was removed under a stream of nitrogen
  2. customthe product dried under vacuum

Sources & evidence

ORD record
ord-8b411f74eff04698b70af1bf42cd6e43
Source dataset
uspto-grants-2013_01
Patent number
US08357706B2

Reaction notes

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