(Diethylamino)sulfur trifluoride → tert-Butyl (2-{7-[3-(4-cyanophenoxy)-2-fluoropropyl]-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl}ethyl)carbamate

HRID 2078439Notes

Reaction equation

HRID 2078439 reaction equation
CCN(S(F)(F)[F:7])CC.[C:10]([C:12]1[CH:41]=[CH:40][C:15]([O:16][CH2:17][C@@H:18](O)[CH2:19][N:20]2[CH2:27][CH:26]3[O:28][CH:22]([CH2:23][N:24]([CH2:29][CH2:30][NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:25]3)[CH2:21]2)=[CH:14][CH:13]=1)#[N:11]>ClCCl>[C:10]([C:12]1[CH:41]=[CH:40][C:15]([O:16][CH2:17][CH:18]([F:7])[CH2:19][N:20]2[CH2:27][CH:26]3[O:28][CH:22]([CH2:23][N:24]([CH2:29][CH2:30][NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:25]3)[CH2:21]2)=[CH:14][CH:13]=1)#[N:11]

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 9876235Azd 7009

Product 1

HCID 15980102tert-Butyl (2-{7-[3-(4-cyanophenoxy)-2-fluoropropyl]-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl}ethyl)carbamateYield 27%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of DAST (0.73 g, 0.0043 mol) in dichloromethane (10 mL) was added tert-butyl (2-{7-[(2S)-3-(4-cyanophenoxy)-2-hydroxypropyl]-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl}ethyl)carbamate (1.50 g, 0.0033 mol; see Preparation R above), in (10 mL) of dichloromethane, dropwise under a nitrogen atmosphere at −65° C. The reaction mixture was slowly brought to RT and stirred at this temperature for 2 h (monitored by HPLC). The reaction mixture was quenched with NaHCO3 (aq.) and extracted with dichloromethane. The organic layer was washed with water and brine and then dried over sodium sulfate. Solvent was evaporated under reduced pressure and the residue was purified by column chromatography over silica gel, using methanol-dichloromethane as the eluent, to yield 0.40 g of the title compound as a brownish, gummy solid.

Workup

  1. customat −65° C
  2. customwas slowly brought to RT
  3. customThe reaction mixture was quenched with NaHCO3 (aq.)
  4. extractionextracted with dichloromethane
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. customSolvent was evaporated under reduced pressure
  8. customthe residue was purified by column chromatography over silica gel

Sources & evidence

ORD record
ord-048ef2d6281d442a83e745ebea55c234
Source dataset
uspto-grants-2011_04
Patent number
US07928225B2

Reaction notes

Loading…