Hydrochloric Acid → Carbamic acid, [(2R)-2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethyl]-, 1,1-dimethylethyl ester

HRID 2117652Notes

Reaction equation

HRID 2117652 reaction equation
B.CSC.CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1.[CH3:26][C:27]1([CH3:48])[O:32][C:31]2[CH:33]=[CH:34][C:35]([C:37](=[O:47])[CH2:38][NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[CH:36][C:30]=2[CH2:29][O:28]1.Cl>C1COCC1.C1(C)C=CC=CC=1>[CH3:26][C:27]1([CH3:48])[O:32][C:31]2[CH:33]=[CH:34][C:35]([C@@H:37]([OH:47])[CH2:38][NH:39][C:40](=[O:46])[O:41][C:42]([CH3:44])([CH3:43])[CH3:45])=[CH:36][C:30]=2[CH2:29][O:28]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 9838490(R)-2-Methyl-CBS-oxazaborolidineHCID 10870948Carbamic acid, [2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxoethyl]-, 1,1-dimethylethyl esterHCID 12423031(Dimethyl sulfide)trihydroboron2×

Product 1

HCID 10881838Carbamic acid, [(2R)-2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethyl]-, 1,1-dimethylethyl esterYield 85.7%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A 2M solution of borane-dimethyl sulphide in THF (28 ml) was added slowly to a 1M solution of (R)-tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaborole in toluene (56 ml) at 0° under nitrogen. A solution of tert-butyl 2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxoethylcarbamate, (108.2 g) in THF (1.3 liters) was added slowly keeping the temperature below 5° followed by 2M solution of borane-dimethyl sulphide in THF (252 ml) over 50 min. After 1 h, 2M HCl (170 ml) was added with cooling and the mixture was partitioned between ethyl acetate and water. The organic layer was washed with saturated NaHCO3 solution and brine and dried (MgSO4). The solution was concentrated and the product purified by chromatography on flash silica gel (800 g), eluting successively with hexane:ethyl acetate (4:1 then 3:1) to give the title compound (93.3 g), LCMS RT=3.31 min.

Workup

  1. customthe temperature below 5°
  2. temperaturewith cooling
  3. customthe mixture was partitioned between ethyl acetate and water
  4. washThe organic layer was washed with saturated NaHCO3 solution and brine
  5. dry with materialdried (MgSO4)
  6. concentrationThe solution was concentrated
  7. customthe product purified by chromatography on flash silica gel (800 g)
  8. washeluting successively with hexane:ethyl acetate (4:1

Sources & evidence

ORD record
ord-ab693d49c90d45338db6d2beaf87ac15
Source dataset
uspto-grants-2008_10
Patent number
US07442719B2

Reaction notes

Loading…