Piperidine → Benzyl 2-(hydroxymethyl)morpholine-4-carboxylate

HRID 429282Notes

Reaction equation

HRID 429282 reaction equation
[OH:1][CH2:2][CH:3]1[O:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]2[C:24]3[CH2:23][C:22]4[C:17](=[CH:18][CH:19]=CC=4)C=3C=CC=2)=[O:10])[CH2:4]1.N1CCCCC1.C(N(C(C)C)CC)(C)C.ClC(OCC1C=CC=CC=1)=O>C(Cl)Cl.CCOC(C)=O>[OH:1][CH2:2][CH:3]1[O:8][CH2:7][CH2:6][N:5]([C:9]([O:11][CH2:12][C:24]2[CH:23]=[CH:22][CH:17]=[CH:18][CH:19]=2)=[O:10])[CH2:4]1

Participants

7

Reactant 4

HCID 8082PiperidineHCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 18354390HCID 18354390, compound

Product 1

HCID 3496524Benzyl 2-(hydroxymethyl)morpholine-4-carboxylateYield 37.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2.20 g of 2-hydroxymethyl-4-fluorenyloxycarbonyl-morpholine in 25 mL of CH2Cl2 was added 1.29 g of piperidine. The mixture was stirred at room temperature for 2 days. Diisopropylethylamine (7.15 g) and 6.30 g of benzyl chloroformate were added and the mixture was stirred overnight at room temperature, then diluted with 100 mL of EtOAc and washed with 50 mL each of 1N HCl, saturated NaHCO3, and brine, dried over MgSO4, and concentrated. The residue was purified by flash chromatography, eluting with a gradient system of 20:1 CH2Cl2-acetone to 9:1 CH2Cl2-acetone, to yield 638 mg of the title compound. 1H NMR (500 MHz, CDCl3): δ7.30-7.40 (m, 5H), 5.15 (ABq, J=12.4 Hz, 2H), 3.93 (br s, 3H), 3.68 (br s, 1H), 3.47-3.63 (m, 3H), 3.02 (br s, 1H), 2.85 (br s, 1H), 1.90 (br s, 0.6H). IR (neat) 3427, 2862, 1693, 1432, 1354, 1236, 1129 cm−1.

Workup

  1. stirringthe mixture was stirred overnight at room temperature
  2. washwashed with 50 mL each of 1N HCl, saturated NaHCO3, and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography
  6. washeluting with a gradient system of 20:1 CH2Cl2-acetone to 9:1 CH2Cl2-acetone

Sources & evidence

ORD record
ord-492b7be5e6e243df8ee00fec559ce1dc
Source dataset
uspto-grants-2001_11
Patent number
US06316444B1

Reaction notes

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