tert-Butyldimethylsilyl trifluoromethanesulphonate → HCID 68447955, compound

HRID 2212492Notes

Reaction equation

HRID 2212492 reaction equation
FC(F)(F)S([O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8])(=O)=O.[CH2:16]([O:23][C@H:24]1[CH2:29][C@@H:28](O)[C@H:27]([NH:31][C@H:32]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH3:33])[CH2:26][CH2:25]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(Cl)Cl>[CH2:16]([O:23][C@@H:24]1[CH2:29][CH2:28][C@@H:27]([NH:31][C@H:32]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH3:33])[C@H:26]([O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8])[CH2:25]1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

4

Reactant 2

HCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 68445057HCID 68445057, compound

Product 1

HCID 68447955HCID 68447955, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyldimethylsilyl trifluoromethanesulfonate (8.8 mL, 38.5 mmole) was added to an ice-cooled, stirred solution of (1R,2R,5R)-5-(benzyloxy)-2-((S)-1-phenylethylamino)-cyclohexanol) (4.8 gm, 14.8 mmole) and TEA (8.2 mL, 59.1 mmole) in dry DCM (250 mL). After 15 min, this was washed with a saturated aq. solution of NaHCO3 and dried (Na2SO4). Removal of the solvent followed by column chromatography (silica gel, step gradient elution with hexane containing 0 to 30% EtOAc) afforded (1R,2R,4R)-4-(benzyloxy)-2-(tert-butyldimethylsilyloxy)-N-((S)-1-phenylethyl)cyclohexanamine (6.2 gm, 95%): MS: 440 (M+H)+; HPLC Ret Time: 2.73 min (YMC Xterra S5 3.0×50 mm column, 3 min gradient, 4 mL/min). A mixture of this material (6.2 gm, 14 mmole), di-tert-butyl dicarbonate (12.2 gm, 56 mmole) and palladium hydroxide (6.5 gm, 20 wt % on carbon, wet) in EtOH (250 mL) was hydrogenated (Paar apparatus, 50 psi H2, 16 hr, RT). Removal of the catalyst and solvent followed by column chromatography (silica gel, step gradient elution with hexane containing 0 to 30% EtOAc) afforded the product (3.3 gm, 68%): [a]25589−19.1 (c 5.9, MeOH); 1H NMR (CDCl3) 0.11 (s, 3H), 0.13 (s, 3H), 0.78 (s, 9H), 1.20 (m, 1H), 1.33 (s, 9H), 1.46 (m, 1H), 1.53 (m, 1H), 1.64 (m, 1H), 1.89 (m, 1H), 2.06 (m, 1H), 2.7 (br s, 1H), 3.36 (m, 1H), 3.36 (m, 1H), 3.67 (m, 1H), 4.38 (m, 1H); MS 346 (M+H).+

Workup

  1. temperaturecooled
  2. washthis was washed with a saturated aq. solution of NaHCO3
  3. dry with materialdried (Na2SO4)
  4. customRemoval of the solvent
  5. washfollowed by column chromatography (silica gel, step gradient elution with hexane containing 0 to 30% EtOAc)

Sources & evidence

ORD record
ord-4e19978e9b82429c82d57b99eda13bc8
Source dataset
uspto-grants-2006_09
Patent number
US07102003B2

Reaction notes

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