Dimethyl dicarbonate → (S)-methyl 2-(methoxycarbonylamino)-2-((S)-tetrahydro-2H-pyran-3-yl)acetate

HRID 1809320Notes

Reaction equation

HRID 1809320 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([C@@H:17]1[CH2:22][CH2:21][CH2:20][O:19][CH2:18]1)[C:13]([O:15][CH3:16])=[O:14])=[O:10])C1C=CC=CC=1.C(OC(OC)=O)(OC)=O>CO.[Pd]>[CH3:1][O:8][C:9]([NH:11][C@@H:12]([C@@H:17]1[CH2:22][CH2:21][CH2:20][O:19][CH2:18]1)[C:13]([O:15][CH3:16])=[O:14])=[O:10]

Participants

5

Reactant 2

HCID 3086Dimethyl dicarbonateHCID 58498907(S)-Methyl 2-(((benzyloxy)carbonyl)amino)-2-((S)-tetrahydro-2H-pyran-3-yl)acetate

Product 1

HCID 58498990(S)-methyl 2-(methoxycarbonylamino)-2-((S)-tetrahydro-2H-pyran-3-yl)acetateYield 87.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

10% Pd/C (69.3 mg, 0.065 mmol) was added to a solution of (S)-methyl 2-(benzyloxycarbonylamino)-2-((S)-tetrahydro-2H-pyran-3-yl)acetate (200 mg, 0.651 mmol) and dimethyl dicarbonate [4525-33-1] (0.104 mL, 0.976 mmol) in MeOH (10 mL). The reaction mixture was vacuum flushed with N2, followed by Hz, and then the reaction was stirred under H2 (55 psi) at rt for 5 h. The reaction mixture was filtered through CELITE®/silica pad and the filtrate was concentrated to a colorless oil. The crude oil was purified by flash silica chromatography (loading solvent: DCM, eluted with 30% EtOAc in hexanes) to yield product (S)-methyl 2-(methoxycarbonylamino)-2-((S)-tetrahydro-2H-pyran-3-yl)acetate (132 mg) as colorless oil. LC-MS retention time 0.92 min; m/z 231.97 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 10 u C18 3.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where Solvent A was 5% MeOH/95% H2O/10 mM ammonium acetate and Solvent B was 5% H2O/95% MeOH/10 mM ammonium acetate. MS data was determined using a MICROMASS® Platform for LC in electrospray mode.

Workup

  1. customflushed with N2
  2. filtrationThe reaction mixture was filtered through CELITE®/silica pad
  3. concentrationthe filtrate was concentrated to a colorless oil
  4. customThe crude oil was purified by flash silica chromatography (loading solvent: DCM, eluted with 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-377c9bf712c14bc6ae1d09091390295a
Source dataset
uspto-grants-2013_01
Patent number
US08362020B2

Reaction notes

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