1,2-Dichloroethane → Benzyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

HRID 579601Notes

Reaction equation

HRID 579601 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]([OH:19])=O)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:21][NH:22][O:23][CH3:24].C(Cl)CCl.C(N(CC)CC)C.Cl>ClCCl>[CH3:24][O:23][N:22]([CH3:21])[C:17]([CH:14]1[CH2:13][CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[CH2:16][CH2:15]1)=[O:19]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 7364891-Carbobenzoxy-4-piperidinecarboxylic Acid

Product 1

HCID 22574154Benzyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

In a 1 L round-bottomed flask, a solution of 1-(benzyloxycarbonyl)piperidine-4-carboxylic acid (21.0 g, 80 mmol) in anhydrous dichloromethane (250 mL) was stirred at room temperature until completely dissolved. After becoming clear, the reaction mixture was cooled to 0° C. and sequentially treated with N,O-dimethylhydroxylamine hydrochloride (9.74 g, 100 mmol), EDC (19.2 g, 100 mmol), and triethylamine (30.4 g, 41.81 mL, 300 mmol). After the additions were complete, the reaction mixture was stirred at room temperature overnight. 1 N HCl (250 mL) was added and after 5 min of additional stirring, the organic phase was separated, washed with 1 N HCl (100 mL), saturated aqueous NaHCO3 (150 mL), dried over MgSO4, filtered and concentrated. Purification by MPLC (100 g column, 50-100% ethyl acetate in heptane) gave benzyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (22.23 g, 91%) as a colorless oil. 1H NMR (CDCl3, 300 MHz) δ 7.42-7.29 (m, 5H), 5.21 (s, 2H), 4.32-4.16 (m, 2H), 3.70 (s, 3H), 3.18 (s, 3H), 2.96-2.78 (m, 3H), 1.80-1.64 (m, 4H). ESI MS found for C16H22N2O4 m/z [307.1 (M+1), 329.2 (M+23)].

Workup

  1. dissolutionuntil completely dissolved
  2. customthe organic phase was separated
  3. washwashed with 1 N HCl (100 mL), saturated aqueous NaHCO3 (150 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by MPLC (100 g column, 50-100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-03d63687c4604caab06c452b9d4fd65c
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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