Isobutanol → HCID 11287845, compound

HRID 381788Notes

Reaction equation

HRID 381788 reaction equation
C[C@@:2]([OH:14])([C@@H:6]([NH2:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3](N)=[O:4].[CH2:15]([OH:19])[CH:16]([CH3:18])[CH3:17]>>[NH2:13][C@@H:6]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C@@H:2]([OH:14])[C:3]([O:19][CH2:15][CH:16]([CH3:18])[CH3:17])=[O:4]

Participants

3

Reactant 2

HCID 6560IsobutanolHCID 86755379HCID 86755379, compound

Product 1

HCID 11287845HCID 11287845, compound

Procedure

To a mixture of crude (2R,3S)-2-hydroxy-3-amine-3-phenylpropionamide (CVII, EXAMPLE 6, 180 mg, 1 mmol) in isobutyl alcohol (2.5 ml) is bubbled anhydrous hydrogen chloride gas until saturated allowing the temperature to rise. The reaction mixture is then heated to 100° overnight. The resulting solution is evaporated to dryness under house vacuum at 50°. The residue is dissolved in water (5 ml), and the aqueous is neutralized with saturated potassium carbonate solution to pH>9. The basic aqueous is extracted with ethyl acetate (15 ml×3). The combined organic phase is dried over magnesium sulfate, filtered and the solvent removed under reduced pressure. The residue is purified by flash chromatography (methanol/dichloromethane, 1/5) to give the title compound, NMR (300 MHz, CDCl3) 7.44-7.28, 4.34, 4.30, 4.00, 1.95 and 0.95 δ; CMR (300 MHz, CDCl3) 173.5, 142.3, 128.5, 127.5, 126.7, 75.0, 71.8, 58.0, 27.6 and 18.9 δ; MS (m/z) 238 (M++1), 165, 136, 118, 107, 106, 104, 91, 79, 77 and 57; HRMS (m/z) calculated for C13H19N1O3+H1=238.1443, observed=238.1441.

Workup

  1. customis bubbled anhydrous hydrogen chloride gas
  2. temperatureThe reaction mixture is then heated to 100° overnight
  3. customThe resulting solution is evaporated to dryness under house vacuum at 50°
  4. dissolutionThe residue is dissolved in water (5 ml)
  5. extractionThe basic aqueous is extracted with ethyl acetate (15 ml×3)
  6. dry with materialThe combined organic phase is dried over magnesium sulfate
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure
  9. customThe residue is purified by flash chromatography (methanol/dichloromethane, 1/5)

Sources & evidence

ORD record
ord-7804cc43eca74a62827cfa4be7948c94
Source dataset
uspto-grants-2001_10
Patent number
US06307064B1

Reaction notes

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