tert-Butanol → Racemic [2-phenyl-3-(toluene-4-sulfonyl)-3-aza-bicyclo[3.1.0]hex-1-yl]-carbamic acid tert-butyl ester

HRID 1295351Notes

Reaction equation

HRID 1295351 reaction equation
[C:1]1([CH:7]2[N:12]([S:13]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=3)(=[O:15])=[O:14])[CH2:11][CH:10]3[C:8]2(C(O)=O)[CH2:9]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([N:28]([CH2:31]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:40])C=CC=CC=1.[C:50]([OH:54])([CH3:53])([CH3:52])[CH3:51]>>[C:50]([O:54][C:31](=[O:40])[NH:28][C:8]12[CH2:9][CH:10]1[CH2:11][N:12]([S:13]([C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)(=[O:14])=[O:15])[CH:7]2[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)([CH3:53])([CH3:52])[CH3:51]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 589073232-Phenyl-3-(toluene-4-sulfonyl)-3-aza-bicyclo[3.1.0]hexane-1-carboxylic acid

Product 1

HCID 69337282Racemic [2-phenyl-3-(toluene-4-sulfonyl)-3-aza-bicyclo[3.1.0]hex-1-yl]-carbamic acid tert-butyl esterYield 34%

Procedure

In a round bottomed flask were combined the starting material racemic 2-phenyl-3-(toluene-4-sulfonyl)-3-aza-bicyclo[3.1.0]hexane-1-carboxylic acid (0.36 g, 1.0 mmol) and tert-butyl alcohol (5 mL). Triethylamine (0.28 mL, 2.0 mmol) and diphenylphosphoryl azide (0.3 mL, 1.4 mmol) were added and the reaction was placed in an 83° C. oil bath and allowed to reflux gently under nitrogen for 16 hours. Most of the tert-butyl alcohol was removed at reduced pressure and the residue was partitioned between saturated sodium bicarbonate solution and EtOAc. The organics were washed with brine, dried over calcium sulfate, filtered and concentrated to an oil which was flash chromatographed on silica gel using 10%-20% ETOAc/Hexanes to give [2-phenyl-3-(toluene-4-sulfonyl)-3-aza-bicyclo[3.1.0]hex-1-yl]-carbamic acid tert-butyl ester (0.14 g, 34%).

Workup

  1. customIn a round bottomed flask were combined
  2. customwas placed in an 83° C.
  3. temperatureto reflux gently under nitrogen for 16 hours
  4. customMost of the tert-butyl alcohol was removed at reduced pressure
  5. customthe residue was partitioned between saturated sodium bicarbonate solution and EtOAc
  6. washThe organics were washed with brine
  7. dry with materialdried over calcium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to an oil which
  10. customchromatographed on silica gel using 10%-20% ETOAc/Hexanes

Sources & evidence

ORD record
ord-e5231f34a1c64d239394f0d41c0253e0
Source dataset
uspto-grants-2007_07
Patent number
US07241798B2

Reaction notes

Loading…