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

HRID 497446Notes

Reaction equation

HRID 497446 reaction equation
C([O:3][C:4]([C@H:6]1[C@H:11]([NH:12][C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[CH2:10][CH2:9][N:8]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:7]1)=[O:5])C.[OH-].[Li+]>O1CCCC1>[C:26]([O:25][C:23]([N:8]1[CH2:9][CH2:10][C@@H:11]([NH:12][C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[C@H:6]([C:4]([OH:5])=[O:3])[CH2:7]1)=[O:24])([CH3:29])([CH3:27])[CH3:28]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 58745548(3R,4R)-4-benzyloxycarbonylamino-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester

Product 1

HCID 58766970(3R,4R)-4-benzyloxycarbonylamino-piperidine-1,3-dicarboxylic acid 1-tert-butyl esterYield 112.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a flask (3R,4R)-4-benzyloxycarbonylamino-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (2.98 g, 7.33 mmol) was dissolved in tetrahydrofuran (120 mL) and lithium hydroxide (15 mL of a 1N aqueous solution, 15 mmol) was added. The mixture was stirred for 68 hours. The reaction was concentrated in vacuo to one-third the original volume. Water (50 mL) and diethyl ether (50 mL) were added and the layers separated. The aqueous layer was extracted with diethyl ether twice (30 mL). The aqueous layer was acidified with aqueous hydrochloric acid (6.5 mL of a 2M solution) and then extracted with ethyl acetate three times (30 mL). The combined organic layers were dried with magnesium sulfate, filtered, and concentrated in vacuo to give a crude white solid (3.11 g) which was used without further purification. 1H NMR (300 MHz, CDCl3), δ: 7.36 (m, 5H), 5.12 (m, 2H), 4.91 (bs, 1H), 4.24 (bs, 1H), 4.09 (bs, 1H), 3.92 (bs, 1H), 3.01 (bs, 1H), 2.87 (m, 1H), 2.44 (m, 1H), 2.05 (bs, 1H), 1.45 (s, 9H), 1.40 (m, 1H).

Workup

  1. concentrationThe reaction was concentrated in vacuo to one-third the original volume
  2. additionWater (50 mL) and diethyl ether (50 mL) were added
  3. customthe layers separated
  4. extractionThe aqueous layer was extracted with diethyl ether twice (30 mL)
  5. extractionthen extracted with ethyl acetate three times (30 mL)
  6. dry with materialThe combined organic layers were dried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d1fa5b0230064953846e7ac5e758e1d8
Source dataset
uspto-grants-2005_09
Patent number
US06949546B2

Reaction notes

Loading…