Methanol → HCID 24752609, compound

HRID 2065768Notes

Reaction equation

HRID 2065768 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:20])=[C:10]([C:21]([OH:23])=[O:22])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.CO.[H][H]>COC(C)(C)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:20])[C@H:10]([C:21]([OH:23])=[O:22])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 887Methanol2×HCID 8471TriethylamineHCID 58985838HCID 58985838, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 24752609HCID 24752609, compound

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

In a glove box an autoclave was charged with 4-o-tolyl-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester (2.5 g), [Ru(OAc)2 ((R)-(2-furyl)-MeOBIPHEP)] (24 mg), triethylamine (1.1 mL) and methanol (25 mL). The asymmetric hydrogenation was run for 60 h at 80° C. under 40 bar of hydrogen. After cooling to room temperature the pressure was released from the autoclave, the methanol solution was diluted with tert-butyl methyl ether (320 mL) and extracted with 1 M aqueous sodium hydroxide solution (2×, 320 mL). The aqueous layer was poured on ice, acidified with ice-cold 2 M aqueous hydrochloric acid solution to pH 1 and extracted with ethyl acetate (3×). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo and triturated from n-heptane to give (3S,4S)-4-o-tolyl-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester as a white solid, MS: 318.2.

Workup

  1. extractionextracted with 1 M aqueous sodium hydroxide solution (2×, 320 mL)
  2. additionThe aqueous layer was poured on ice
  3. extractionextracted with ethyl acetate (3×)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customtriturated from n-heptane

Sources & evidence

ORD record
ord-e768bf9e75ac4538b54eebc55e2d7507
Source dataset
uspto-grants-2012_10
Patent number
US08288541B2

Reaction notes

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