1,2-Dichloroethane → tert-Butyl 3-(methoxy(methyl)carbamoyl)azetidine-1-carboxylate

HRID 221203Notes

Reaction equation

HRID 221203 reaction equation
[C:1]([N:8]1[CH2:11][CH:10]([C:12]([OH:14])=O)[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl.[CH3:16][NH:17][O:18][CH3:19].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH3:19][O:18][N:17]([CH3:16])[C:12]([CH:10]1[CH2:9][N:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH2:11]1)=[O:14]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 27559811-Boc-Azetidine-3-carboxylic acid

Product 1

HCID 21306970tert-Butyl 3-(methoxy(methyl)carbamoyl)azetidine-1-carboxylateYield 99.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-Boc-azetidine-3-carboxylic acid (5.0 g, 24.9 mmol) in DMF (40 mL) was added N,O-dimethylhydroxylamine hydrochloride (2.89 g, 29.8 mmol), EDC (5.55 g, 29.8 mmol), HOBt (3.36 g, 24.9 mmol) and DIPEA (9.82 mL, 54.7 mmol). The reaction was stirred at room temperature for 20 h. The reaction was diluted with water (150 mL) and extracted with EtOAc (2×100 mL). The combined organic extracts were washed with water (150 mL) and brine (150 mL), dried over MgSO4 and concentrated under vacuum to afford 4 as a clear colorless oil (6.06 g, 99%); 1H-nmr (400 MHz, CDCl3) δ 4.21-4.11 (m, 2H), 4.05 (t, J=8.0 Hz, 2H), 3.66 (s, 3H), 3.68-3.59 (m, 1H), 3.21 (s, 3H), 1.44 (s, 9H); m/z 189.1 [M−tBu].

Workup

  1. extractionextracted with EtOAc (2×100 mL)
  2. washThe combined organic extracts were washed with water (150 mL) and brine (150 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-034763a375b04c8ab96ad595a991f1dc
Source dataset
uspto-grants-2012_06
Patent number
US08207155B2

Reaction notes

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