Methanol → tert-Butyl 2-(2-(6-(methylsulfonamido)-4-oxospiro[chroman-2,4'-piperidine]-1'-yl)ethoxy)ethylcarbamate

HRID 1093902Notes

Reaction equation

HRID 1093902 reaction equation
C(N(CC)C(C)C)(C)C.Br[CH2:11][CH2:12][O:13][CH2:14][CH2:15][NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20].Cl.[O:25]=[C:26]1[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([NH:41][S:42]([CH3:45])(=[O:44])=[O:43])[CH:39]=2)[O:34][C:28]2([CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[CH2:27]1.CO>CN(C=O)C.ClCCl.C(OCC)(=O)C.O>[CH3:45][S:42]([NH:41][C:38]1[CH:39]=[C:40]2[C:35](=[CH:36][CH:37]=1)[O:34][C:28]1([CH2:29][CH2:30][N:31]([CH2:11][CH2:12][O:13][CH2:14][CH2:15][NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:32][CH2:33]1)[CH2:27][C:26]2=[O:25])(=[O:43])=[O:44]

Participants

9

Reactant 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 19045253N-(4-Oxospiro[chroman-2,4'-piperidine]-6-yl)methanesulfonamide hydrochloride2×HCID 22712752tert-butyl N-[2-(2-bromoethoxy)ethyl]carbamate

Product 1

HCID 57903876tert-Butyl 2-(2-(6-(methylsulfonamido)-4-oxospiro[chroman-2,4'-piperidine]-1'-yl)ethoxy)ethylcarbamateYield 134.9%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of N,N-diisopropylethylamine (1.3 mL, 7.5 mmol), tert-butyl 2-(2-bromoethoxy)ethyl-carbamate (4, 0.59 g, 2.2 mmol), and N-(4-oxospiro[chroman-2,4′-piperidine]-6-yl)methanesulfon-amide hydrochloride (11, 0.5 g, 1.4 mmol) in 10 mL of anhydrous DMF was stirred at 60-65° C. After ˜24 hours TLC (silica gel, 10% methanol in dichloromethane, UV visualization) showed almost complete disappearance of starting amine 11 (Rf=0.02−0.06) and appearance of one major new product (Rf=0.35-0.45). The reaction was allowed to cool to room temperature and 10 mL of water was added. The resulting mixture was transferred to a separatory funnel with the aid of ethyl acetate and the layers were separated. The aqueous layer was extracted with 20 mL of ethyl acetate. The organic extracts were combined, washed successively with 10 mL portions of water and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure on a rotary evaporator followed by high vacuum to provide 0.94 g of orange-brown oil.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted with 20 mL of ethyl acetate
  3. washwashed successively with 10 mL portions of water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure on a rotary evaporator

Sources & evidence

ORD record
ord-0a3d688279de42bb9d46e412936e6f85
Source dataset
uspto-grants-2012_03
Patent number
US08133695B2

Reaction notes

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