1,2-Dichloroethane → (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

HRID 1053772Notes

Reaction equation

HRID 1053772 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([C:16]([OH:18])=O)[S:10][C:11]=2[C:12]([F:15])([F:14])[F:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[Si:33]([O:40][CH2:41][CH2:42][N:43]([C@H:51]1[C:59]2[C:54](=[C:55]([C:60](=[NH:63])[NH:61]O)[CH:56]=[CH:57][CH:58]=2)[CH2:53][CH2:52]1)[C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34]>CN(C=O)C>[Si:33]([O:40][CH2:41][CH2:42][N:43]([C@H:51]1[C:59]2[C:54](=[C:55]([C:60]3[N:63]=[C:16]([C:9]4[S:10][C:11]([C:12]([F:13])([F:14])[F:15])=[C:7]([C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[CH:8]=4)[O:18][N:61]=3)[CH:56]=[CH:57][CH:58]=2)[CH2:53][CH2:52]1)[C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])([C:36]([CH3:37])([CH3:38])[CH3:39])([CH3:35])[CH3:34]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 27833724-Phenyl-5-(trifluoromethyl)thiophene-2-carboxylic acidHCID 178453848HCID 178453848, compound

Product 1

HCID 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)carbamateYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

Prepared using General Procedure 2. To a solution of 4-phenyl-5-(trifluoromethyl)thiophene-2-carboxylic acid (0.109 g, 0.4 mmol) in DMF (3.0 mL) was added HOBt (0.088 g, 0.57 mmol) and EDC (0.109 g, 0.57 mmol) at room temperature. The reaction mixture was stirred for 0.5 h until the complete formation of the HOBt-acid complex. (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl(4-(N-hydroxycarbamimidoyl)-2,3-dihydro-1H-inden-1-yl)carbamate INT-61 (0.200 g, 0.44 mmol) was added and the mixture was stirred at room temperature for 0.5 h until the formation of the intermediate (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl(4-(N-(4-phenyl-5-(trifluoromethyl)thiophene-2-carbonyloxy) carbamimidoyl)-2,3-dihydro-1H-inden-1-yl) carbamate was observed. The reaction mixture was heated at 85° C. for 4 h. Upon cooling, the mixture was extracted with DCM and brine. The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to produce a brown oil. The crude product was purified by silica gel flash chromatography (MeOH/DCM) to yield 0.108 g (40%) of (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxa-diazol-3-yl)-2,3-dihydro-1H-inden-1-yl)carbamate INT-63 as a light yellow oil. LCMS-ESI (m/z) calculated for C35H42F3N3O4SSi: 685.9; found 411.0 [M+H−tert-butyl 2-(tert-butyldimethylsilyloxy)ethylcarbamate]+, tR=4.01 min.

Workup

  1. customPrepared
  2. addition(0.200 g, 0.44 mmol) was added
  3. temperatureUpon cooling
  4. extractionthe mixture was extracted with DCM and brine
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto produce a brown oil
  9. customThe crude product was purified by silica gel flash chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-d7248a707dfd43e6a5de1933cb653753
Source dataset
uspto-grants-2016_07
Patent number
US09394264B2

Reaction notes

Loading…