HCID 58498828, compound → (S)-Methyl 2-(((benzyloxy)carbonyl)amino)-2-((S)-tetrahydro-2H-pyran-3-yl)acetate

HRID 625553Notes

Reaction equation

HRID 625553 reaction equation
[CH2:1]([O:8][C:9]([NH:11]/[C:12](=[C:17]1\[CH2:18][O:19][CH2:20][CH2:21][CH2:22]\1)/[C:13]([O:15][CH3:16])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>CO.[B-](F)(F)(F)F.C[C@H]1CC[C@H](C)P1CCP1[C@@H](C)CC[C@@H]1C.C1CC=CCCC=C1.[Rh]>[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])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 1

HCID 58498828HCID 58498828, compound

Product 1

HCID 58498907(S)-Methyl 2-(((benzyloxy)carbonyl)amino)-2-((S)-tetrahydro-2H-pyran-3-yl)acetateYield 65.4%

Reagents, catalysts & solvents 2

HCID 129644171,2-Bis[(2S,5S)-2,5-dimethylphospholano]ethane(cyclooctadiene)rhodium(I) tetrafluoroborateCatalystHCID 887MethanolSolvent

Procedure

(−)-1,2-Bis((2S,5S)-2,5-dimethylphospholano)ethane(cyclooctadiene)-rhodium(I)tetrafluoroborate (28.2 mg, 0.051 mmol) was added to a stirred solution of (Z)-methyl 2-(benzyloxycarbonylamino)-2-(2H-pyran-3(4H,5H,6H)-ylidene)acetate (310 mg, 1.015 mmol) in MeOH (10 mL) and the mixture was vacuum flushed with N2, followed by H2, and then the reaction was stirred under H2 (60 psi) at rt for 2 d. The reaction mixture was concentrated and the residue was purified by flash silica chromatography (loading solvent: DCM, eluted with 20% EtOAc in hexanes) to yield (S)-methyl 2-(benzyloxycarbonylamino)-2-((S)-tetrahydro-2H-pyran-3-yl)acetate (204 mg) as clear colorless oil. LC-MS retention time 1.437 min; m/z 307.89 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 10u 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. 1H NMR (400 MHz, chloroform-d) δ ppm 7.30-7.46 (m, 5H), 5.32 (d, J=8.8 Hz, 1H), 5.12 (s, 2H), 4.36 (dd, J=8.9, 5.6 Hz, 1H), 3.84-3.98 (m, 2H), 3.77 (s, 3H), 3.28-3.37 (m, 1H), 3.23 (dd, J=11.3, 10.5 Hz, 1H), 2.04-2.16 (m, 1H), 1.61-1.75 (m, 3H), 1.31-1.43 (m, 1H).

Workup

  1. customflushed with N2
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue was purified by flash silica chromatography (loading solvent: DCM, eluted with 20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-78d6c845421a41f2a3df378fcc5a561e
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

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