Ethanol → 1-Piperidinecarboxylic acid, 4-(ethoxymethyl)-4-hydroxy-, 1,1-dimethylethyl ester

HRID 2202338Notes

Reaction equation

HRID 2202338 reaction equation
[H-].[Na+].[O:3]1[C:5]2([CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]2)[CH2:4]1.[CH3:18][CH2:19][OH:20]>>[CH2:19]([O:20][CH2:4][C:5]1([OH:3])[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1)[CH3:18]

Participants

4

Reactant 3

HCID 702EthanolHCID 24758Sodium hydrideHCID 22135564tert-Butyl 1-oxa-6-azaspiro(2.5)octane-6-carboxylate

Product 1

HCID 722082611-Piperidinecarboxylic acid, 4-(ethoxymethyl)-4-hydroxy-, 1,1-dimethylethyl ester

Procedure

To anhydrous EtOH (20 mL) was added slowly NaH (124 mg, 52 mmol) at 0° C., and after the addition was complete the mixture was stirred for 1.5 h. Then tert-butyl 1-oxa-6-azaspiro[2.5]octane-6-carboxylate (9B, 45 mmol) was added, and the resulting mixture was stirred at 50° C. for 1 h, when TLC showed that s.m. was consumed. Then the mixture was neutralized with 1N aq. HCl, and concentrated. The residue was purified by prep-TLC to give the desired product 9C as colorless oil (600 mg)1H NMR (METHANOL-d4) δ: 3.78 (d, J=12.6 Hz, 2H), 3.51 (q, J=7.0 Hz, 2H), 3.22-3.29 (m, 2H), 3.15 (br. s., 2H), 1.48-1.60 (m, 4H), 1.43 (s, 9H), 1.18 (t, J=7.0 Hz, 3H).

Workup

  1. additionafter the addition
  2. stirringthe resulting mixture was stirred at 50° C. for 1 h
  3. customwas consumed
  4. concentrationconcentrated
  5. customThe residue was purified by prep-TLC

Sources & evidence

ORD record
ord-d777a18fcd5646ceadc5ed5f6f339fe6
Source dataset
uspto-grants-2016_06
Patent number
US09365545B2

Reaction notes

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