Water → (3R,4R)-4-benzyloxycarbonylamino-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester

HRID 1169194Notes

Reaction equation

HRID 1169194 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[C@H:11]([NH2:12])[CH2:10][CH2:9][N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7]1)=[O:5])[CH3:2].C(N(CC)CC)C.Cl[C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29].O>ClCCl>[CH2:1]([O:3][C:4]([C@H:6]1[C@H:11]([NH:12][C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])[CH2:10][CH2:9][N:8]([C:13]([O:15][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:14])[CH2:7]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 58745614(3R,4R)-1-tert-butyl 3-ethyl 4-aminopiperidine-1,3-dicarboxylate

Product 1

HCID 58745548(3R,4R)-4-benzyloxycarbonylamino-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl esterYield 51.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a dry flask (3R,4R)-4-aminopiperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (3.07 g, 11.3 mmol) was dissolved in dichloromethane (100 mL) and triethylamine (2.1 mL, 15.1 mmol) and benzyl chloroformate (2.0 mL, 12.6 mmol) were added. The mixture was stirred for 22 hours. Water (30 mL) was added and the layers separated. The aqueous layer was extracted with dichloromethane (30 mL). The combined organic layers were dried with magnesium sulfate, filtered, and concentrated in vacuo to give a crude oil (4.91 g). Purification by flash column chromatography (40% ethyl acetate/hexanes) provided a colorless oil (2.37 g, 51%). 1H NMR (300 MHz, CDCl3), δ: 7.33 (m, 5H), 5.08 (s, 2H), 4.71 (s, 1H), 4.12 (m, 4H), 3.90 (m, 1H), 2.98 (bs, 1H), 2.85 (t, 1H, J=13), 2.37 (m, 1H), 2.06 (d, 1H, J=7), 1.45 (s, 9H), 1.37 (m, 1H), 1.20 (t, 3H, J=7).

Workup

  1. customthe layers separated
  2. extractionThe aqueous layer was extracted with dichloromethane (30 mL)
  3. dry with materialThe combined organic layers were dried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a crude oil (4.91 g)
  7. customPurification by flash column chromatography (40% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9e5ff0b7a5904e9f9096e4741ceb0b4a
Source dataset
uspto-grants-2003_09
Patent number
US06627629B2

Reaction notes

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