Triethylamine → Tert-butyl trans-4-[(cyclopropylcarbonyl)amino]-3-hydroxypiperidine-1-carboxylate

HRID 1427356Notes

Reaction equation

HRID 1427356 reaction equation
C(N(CC)CC)C.[CH:8]1([C:11](Cl)=[O:12])[CH2:10][CH2:9]1.[NH2:14][C@@H:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][C@H:16]1[OH:28]>O1CCCC1>[CH:8]1([C:11]([NH:14][C@@H:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:17][C@H:16]2[OH:28])=[O:12])[CH2:10][CH2:9]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chlorideHCID 10727458rac-tert-butyl (3R,4R)-4-amino-3-hydroxypiperidine-1-carboxylate

Product 1

HCID 117678136Tert-butyl trans-4-[(cyclopropylcarbonyl)amino]-3-hydroxypiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (4.85 mL, 34.8 mmol) and cyclopropanecarbonyl chloride (3.18 mL, 35.0 mmol) were added to a 0° C. solution of tert-butyl trans-4-amino-3-hydroxypiperidine-1-carboxylate (7.52 g, 34.8 mmol) in tetrahydrofuran (100 mL), and the reaction was allowed to warm to room temperature and stir for 18 hours. After concentration in vacuo, the crude product was diluted with ethyl acetate, insoluble material was removed by filtration, and the solids were washed with ethyl acetate (3×50 mL). The combined filtrates were concentrated under reduced pressure, and the residue was purified by silica gel chromatography (Gradient: 0% to 5% methanol in ethyl acetate) to afford the product as a solid. Yield: 1.30 g, 4.57 mmol, 13%. LCMS m/z 285.6 [M+H]+. 1H NMR (400 MHz, CDCl3), observed peaks: δ 5.79 (br d, J=5 Hz, 1H), 4.21-4.34 (br m, 1H), 4.03-4.21 (br m, 1H), 3.70-3.79 (m, 1H), 3.34-3.42 (m, 1H), 2.66-2.79 (br m, 1H), 2.59 (br dd, J=12, 11 Hz, 1H), 1.88-1.96 (m, 1H), 1.46 (s, 9H), 1.37-1.44 (m, 1H), 1.01-1.05 (m, 2H), 0.77-0.87 (m, 2H).

Workup

  1. concentrationAfter concentration in vacuo
  2. additionthe crude product was diluted with ethyl acetate, insoluble material
  3. customwas removed by filtration
  4. washthe solids were washed with ethyl acetate (3×50 mL)
  5. concentrationThe combined filtrates were concentrated under reduced pressure
  6. customthe residue was purified by silica gel chromatography (Gradient: 0% to 5% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-302289f43f6342aab046ee4e3ddefea5
Source dataset
uspto-grants-2015_01
Patent number
US08933224B2

Reaction notes

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