Dichloromethane → Isobutyl chloroformate

HRID 1720017Notes

Reaction equation

HRID 1720017 reaction equation
[N:1]1([C:10]([O:12][CH2:13][C:14]2[CH:19]=CC=C[CH:15]=2)=[O:11])[CH2:9][CH2:8][CH2:7][CH2:6][C@H:2]1C(O)=O.[CH2:20](Cl)[Cl:21]>>[CH2:13]([O:12][C:10]([Cl:21])=[O:11])[CH:14]([CH3:19])[CH3:15].[CH3:20][CH:7]1[CH2:6][CH2:2][NH:1][CH2:9][CH2:8]1

Participants

4

Reactant 2

HCID 6344DichloromethaneHCID 688345(S)-1-N-Cbz-Pipecolinic acid

Product 2

HCID 62365Isobutyl chloroformateHCID 693814-Methylpiperidine

Procedure

A suspension of 1.300 g (4.94 mmoles) of N-benzyloxycarbonyl-(L)-pipecoline-2-carboxylic acid (abbreviation Z-(L)-PipOH, prepared from (L)-pipecholine-2carboxylic acid (Aldrich) according to the method of Wunsch) in 60 ml of dry methylene chloride (CH2Cl2) was brought under argon atmosphere to a temperature of approximately -20° C. On stabilization of the temperature, the following were added in quick succession: 0. 670 ml (5.13 mmoles) of isobutylchloroformate (IBCF) and 0.630 ml (5.18 mmoles) of 4-methylpiperidine (NMP), leaving the system under stirring for approximately 2 minutes. A solution, pre-cooled to approximately -15 ° C. for 30 minutes, of 1.730 g (4.70 mmoles) of (L) -Leu-(L) TrpOMe. HCl (Novabiochem) and 0.580 ml (4.77 mmoles) of NMP in 25 ml of anhydrous N,N-dimethylformamide (DMF) was then added, leaving, under stirring and static argon, the temperature free to rise to room temperature. After approximately 3,5 hours of reaction, the white precipitate was filtered away and washed with a little CH 2 Cl2. The latter was put back into the pale yellow coloured organic solution, which was extracted in succession using 5% NaHCO3 (3×30 ml); saturated aqueous NaCl (2×30 ml); 4% KHSO4 (3×30 ml) and finally saturated aqueous NaCl (3×30 ml), discarding the aqueous phases. The organic phase extracted, of a pale yellow colour, was left in a cold chamber under argon and on anhydrous Na2SO4 for 12 hours. The desiccant was then filtered away and the organic solution, concentrated to a small volume, was added dropwise under stirring to 200 ml of dry petroleum ether (30/50), obtaining an abundant milk-white precipitate which, after several hours at rest in a cold chamber, was filtered and left for 24 hours under vacuum on P2O5 2.300 g (84.8%) of an analytically pure white solid were recovered.

Workup

  1. customprepared from (L)-pipecholine-2carboxylic acid (Aldrich)
  2. customwas brought under argon atmosphere to a temperature of approximately -20° C
  3. additionOn stabilization of the temperature, the following were added in quick succession

Sources & evidence

ORD record
ord-6b6b1c30a9234e9381e4b6c2ba1c861c
Source dataset
uspto-grants-1996_04
Patent number
US05504071

Reaction notes

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