Formaldehyde → Tert-butyl 3-hydroxy-1-oxo-1-phenylpropan-2-ylcarbamate

HRID 2054767Notes

Reaction equation

HRID 2054767 reaction equation
[O:1]=[C:2]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:3][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].[C:18]([O-])(O)=[O:19].[Na+].C=O.[Na+].[Cl-]>CCO>[OH:19][CH2:18][CH:3]([NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:8])[CH3:9])[C:2](=[O:1])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 5234Sodium ChlorideHCID 516892Sodium BicarbonateHCID 11230079tert-butyl N-(2-oxo-2-phenylethyl)carbamate

Product 1

HCID 59656741Tert-butyl 3-hydroxy-1-oxo-1-phenylpropan-2-ylcarbamateYield 173.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

tert-butyl 1-oxo-1-phenylethan-2-ylcarbamate (18) (2.4 g, 10.0 mmol, 1.0 equiv.) was added to a 100 mL RBF followed by EtOH (41 mL, 200 proof). Next, a 0.5 M solution of NaHCO3 (420 mg, 5.0 mmol, 0.5 equiv.) was added followed by a 37% solution of formaldehyde (1.2 mL, 15.0 mmol, 1.5 equiv.). The solution was stirred at rt. for 6 days and transferred to a separatory funnel with a 1.0 M solution of NaCl (5.0 g, 85.5 mmol). The solution was extracted with CH2Cl2 (5×50 mL). The organic layer was dried over Na2SO4, concentrated on a rotary evaporator, and dried under vacuum to give a crude light yellow oil. The residue was purified by flash column chromatography (30% EtOAc/hexanes) to give 2.3 g (88%) of 19 as a colorless oil which crystallized to a white solid. (Note: It is essential to use a 100 mL RBF for full vortex stirring over the entire reaction period) Rf=0.16 (30% EtOAc/Hexanes); mp=69-71° C.; IR (film) 3420, 2976, 2931, 1683, 1503, 1366, 1165, 1061 cm−1; 1H NMR (500 MHz, CDCl3) δ 8.00 (d, J=7.0 Hz, 2H, Ph-H), 7.60 (t, J=7.0 Hz, 1H, Ph-H), 7.48 (t, J=7.0 Hz, 2H, Ph-H), 5.96 (d, J=6.0 Hz, 1H, carbamate-NH), 5.36 (br s, 1H, Boc-NH—CH), 4.00 (m, 1H, CH—CH2), 3.86 (m, 1H, CH—CH2), 3.29 (br s, 1H, CH2—OH), 1.45 (s, 9H, t-butyl-CH3); 13C (125 MHz, CDCl3) δ 197.4, 156.3, 134.6, 134.1, 129.0, 128.9, 80.5, 64.7, 58.1, 28.4; LRMS (ESI-MS m/z): Mass calcd for C14H19NNaO4 [M+Na]+, 288.29. Found 288. Anal. calcd for C14H19NO4: C, 63.38; H, 7.22; N, 5.28 Found: C, 63.22; H, 7.25; N, 5.28.

Workup

  1. extractionThe solution was extracted with CH2Cl2 (5×50 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated on a rotary evaporator
  4. customdried under vacuum
  5. customto give a crude light yellow oil
  6. customThe residue was purified by flash column chromatography (30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e75fa4f66f7345de8526e83a99d83b44
Source dataset
uspto-grants-2008_02
Patent number
US07329775B2

Reaction notes

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