1,2-Dichloroethane → Tert-butyl 3-(methoxy(methyl)carbamoyl)-8-azabicyclo[3.2.1]octane-8-carboxylate

HRID 1778577Notes

Reaction equation

HRID 1778577 reaction equation
C(Cl)CCl.[C:5]([O:9][C:10]([N:12]1[C@H:17]2[CH2:18][CH2:19][C@@H:13]1[CH2:14][CH:15]([C:20](O)=[O:21])[CH2:16]2)=[O:11])([CH3:8])([CH3:7])[CH3:6].Cl.[CH3:24][NH:25][O:26][CH3:27].C(N(CC)CC)C>CN(C1C=CN=CC=1)C.ClCCl.O>[CH3:27][O:26][N:25]([CH3:24])[C:20]([CH:15]1[CH2:16][CH:17]2[N:12]([C:10]([O:9][C:5]([CH3:6])([CH3:7])[CH3:8])=[O:11])[CH:13]([CH2:19][CH2:18]2)[CH2:14]1)=[O:21]

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 50999080exo-8-Boc-8-azabicyclo(3.2.1)octane-3-carboxylic acid

Product 1

HCID 89514318Tert-butyl 3-(methoxy(methyl)carbamoyl)-8-azabicyclo[3.2.1]octane-8-carboxylateYield 73%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

EDC (2.99 g, 15.6 mmol) was added portion wise to a stirred solution of (1R,5S)-8-(tert-butoxycarbonyl)-8-azabicyclo[3.2.1]octane-3-carboxylic acid, (2.0 g, 7.8 mmol), DMAP (10 mg), and N,O-dimethylhydroxylamine hydrochloride (1.52 g, 15.6 mmol) in dichloromethane (20 mL). Triethylamine (4.37 mL, 31.33 mmol) was added dropwise, and the reaction mixture was stirred at room temperature overnight. The resulting solution was poured into water, and extracted with ethyl acetate (3×). The combined organic phase was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give tert-butyl 3-(methoxy(methyl)carbamoyl)-8-azabicyclo[3.2.1]octane-8-carboxylate (1.7 g, 73%) as a colorless oil, which was used without further purification; m/z for C15H26N2O4 expected 298.2. found 321.3 (M+Na)+, 299.3 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. washThe combined organic phase was washed with saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1a7af380caba4311a87ab11c2e25896b
Source dataset
uspto-grants-2016_02
Patent number
US09266908B2

Reaction notes

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