Glycine tert-butyl ester → Tert-butyl 2-(2,2-dimethylchroman-6-sulfonamido)acetate

HRID 1805949

Reaction equation

HRID 1805949 reaction equation
[CH3:1][C:2]1([CH3:16])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([S:12](Cl)(=[O:14])=[O:13])[CH:8]=2)[O:3]1.[NH2:17][CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20]>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCOC(C)=O>[CH3:1][C:2]1([CH3:16])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([S:12]([NH:17][CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])(=[O:14])=[O:13])[CH:8]=2)[O:3]1

Participants

6

Reactant 2

HCID 151417Glycine tert-butyl esterHCID 27797742,2-Dimethyl-6-Chromanesulfonyl Chloride

Product 1

HCID 58409094Tert-butyl 2-(2,2-dimethylchroman-6-sulfonamido)acetateYield 88%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

To the solution of 2,2-dimethylchroman-6-sulfonyl chloride (3.165 g, 10.92 mmol) in DCM (50 mL) at −30° C. was added tert-butyl 2-aminoacetate (2.308 mL, 16.39 mmol), Hunig'sBase (3.82 mL, 21.85 mmol), and catalytic amount of DMAP. The mixture was stirred at 25° C. overnight while the reddish orange color of the reaction mixture turned bright yellow. The crude reaction mixture was diluted with EtOAc, washed with dilute aqueous hydrochloric acid solution, then aqueous NaHCO3 solution and brine. The organic layer was dried over MgSO4 and removed on a rotavapor to give a creamy powder. The crude material was purified by silica chromatography (15-30% EtOAc/Hexanes) to yield 3.6 grams of an off white powder (88%). 1H NMR (500 MHz, CDCl3) δ 7.58 (d, J=2.1 Hz, 1H), 7.55 (dd, J=8.6, 2.3 Hz, 1H), 6.81 (t, J=10.6 Hz, 1H), 4.90 (s, 1H), 3.64 (d, J=5.1 Hz, 2H), 2.81 (t, J=6.7 Hz, 2H), 1.81 (t, J=6.7 Hz, 2H), 1.35 (s, 9H), 1.34 (s, 6H). LRMS [ESI, (M−H)−] m/z calcd for C17H24NO5S 354.14, found 354.2.

Workup

  1. customThe crude reaction mixture
  2. washwashed with dilute aqueous hydrochloric acid solution
  3. dry with materialThe organic layer was dried over MgSO4
  4. customremoved on a rotavapor
  5. customto give a creamy powder
  6. customThe crude material was purified by silica chromatography (15-30% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-af38c9975eda47a49ab16f97631878bd
Source dataset
uspto-grants-2013_01
Patent number
US08354548B2

Linked notes

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