Hydrochloric Acid → HCID 59656749, compound

HRID 1170809Notes

Reaction equation

HRID 1170809 reaction equation
[O:1]=[C:2]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH:3]([NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])[CH3:4].[CH2:19]=[O:20].C([O-])([O-])=O.[K+].[K+].Cl.[Na+].[Cl-]>CCO>[OH:20][CH2:19][C:3]([NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])([CH3:4])[C:2](=[O:1])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 5234Sodium ChlorideHCID 11430Potassium CarbonateHCID 11482058HCID 11482058, compound

Product 1

HCID 59656749HCID 59656749, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
35 °C

Procedure

tert-butyl 1-oxo-1-phenylpropan-2-ylcarbamate (40) (1.3 g, 5.0 mmol, 1.0 equiv.) was added to a 100 mL RBF followed by EtOH (39 mL). Next, a 37% solution of formaldehyde (8.1 mL, 100 mmol, 20.0 equiv.) was added to the reaction mixture and the solution heated to 35° C. Finally, a 0.5 M solution of K2CO3 (350 mg, 2.5 mmol, 5.0 mL dH2O, 0.5 equiv.) was added to the reaction flask and the solution stirred vigorously for 24 h. The solution was neutralized with 1% HCl, transferred to a separatory funnel with a 1.7 M solution of NaCl (5.0 g, 85.0 mmol, 50 mL H2O), and extracted with CH2Cl2 (5×50 mL). The organic layers were combined and dried over Na2SO4. The resulting solution was concentrated on a rotary evaporator and dried under vacuum to give a crude oil. The residue was purified by flash column chromatography (30% EtOAc/Hexanes) to give 1.1 g (79%) of 41 as a colorless oil. Rf=0.29 (50% EtOAc/Hexanes); IR (film) 3352, 2977, 1684, 1367, 1166 cm−1; 1H NMR (500 MHz, CDCl3) δ Major Rotamer: 8.00 (br s, 2H, Ph-H), 7.42 (br s, 3H, Ph-H), 5.87 (br s, 1H, carbamate-NH), 5.49 (br s, 1H, Boc-NH—CH), 4.12 (m, 2H, C—CH2), 3.76 (m, 2H, C—CH2), 3.32 (br s, 2H, CH2—OH), 1.63 (s, 3H, C—CH3), 1.26 (s, 9H, t-butyl-CH3). Minor Rotamer: 8.15 (br s, 2H, Ph-H), 7.51 (br s, 3H, Ph-H), 5.82 (br s, 1H, carbamate-NH), 3.09 (br s, 2H, CH2—OH), 1.09 (s, 9H, t-butyl-CH3); 13C NMR (125 MHz, CDCl3) Major Rotamer: δ 202.8, 155.1, 132.9, 128.5, 128.3, 80.5, 67.9, 64.4, 28.2, 21.6; LRMS (ESI-MS m/z): Mass calcd for C15H21NNaO4 [M+Na]+, 302.32. Found 302.

Workup

  1. extractionextracted with CH2Cl2 (5×50 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationThe resulting solution was concentrated on a rotary evaporator
  4. customdried under vacuum
  5. customto give a crude oil
  6. customThe residue was purified by flash column chromatography (30% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-1ff71241e6b24afba9ce5f7a7baf16a1
Source dataset
uspto-grants-2010_11
Patent number
US07829304B2

Reaction notes

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