Citric Acid → HCID 178445781, compound

HRID 2404095Notes

Reaction equation

HRID 2404095 reaction equation
[C:1]([CH:5]1[CH2:10][CH2:9][CH:8]([O:11][C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([CH:22]=O)[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[NH2:24][CH2:25][C:26]([F:31])([F:30])[C:27]([OH:29])=[O:28].C(O)C.C([BH3-])#N.[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>>[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([CH2:22][NH:24][CH2:25][C:26]([F:31])([F:30])[C:27]([OH:29])=[O:28])[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 5

HCID 311Citric AcidHCID 702EthanolHCID 27564053-Amino-2,2-difluoropropanoic acidHCID 5003444Sodium cyanoborohydrideHCID 866684126-(trans-4-Tert-butylcyclohexyloxy)-2-naphthaldehyde

Product 1

HCID 178445781HCID 178445781, compoundYield 64%

Procedure

A solution of 6-(4-tert-Butyl-cyclohexyloxy)-naphthalene-2-carbaldehyde (150 mg, 0.483 mmol) and 3-amino-2,2-difluoro-propionic acid (60.4 mg, 0.483 mmol) in ethanol (0.7 mL, 10 mmol) was heated to reflux for 2 h. The yellow solution was then cooled to room temperature and sodium cyanoborohydride (36.4 mg, 0.580 mmol) was added to the stirring solution. The resulting mixture was heated to reflux for 1 h. After cooling to room temperature, citric acid was added, and the solvent removed under vacuum. The resulting solid was suspended in water and collected via filtration. The filtrate was washed thoroughly with water (4×), ether (3×), and hexane (3×). The resulting solid was dried on the filter to give the title compound as a white solid (128.8 mg, 64%). 1H NMR (400 MHz, CDCl3) δ: 7.92 (s, 1H), 7.87 (d, J=8.5 Hz, 1H), 7.82 (d, J=9.1 Hz, 1H), 7.52 (dd, J=8.4, 1.8 Hz, 1H), 7.30 (d, J=2.2 Hz, 1H), 7.19 (dd, J=9.0, 2.4 Hz, 1H), 4.45 (s, 2H), 4.40 (m, 1H), 3.61 (t, J=13.8 Hz, 2H), 2.28-2.31 (m, 2H), 1.92-1.95 (m, 2H), 1.49-1.14 (m, 5H), 0.94 (s, 9H).

Workup

  1. temperatureto reflux for 2 h
  2. temperatureThe resulting mixture was heated
  3. temperatureto reflux for 1 h
  4. temperatureAfter cooling to room temperature
  5. customthe solvent removed under vacuum
  6. filtrationcollected via filtration
  7. washThe filtrate was washed thoroughly with water (4×), ether (3×), and hexane (3×)
  8. customThe resulting solid was dried on the
  9. filtrationfilter

Sources & evidence

ORD record
ord-e01458d57f9e402b90a2de4720198b15
Source dataset
uspto-grants-2014_08
Patent number
US08802659B2

Reaction notes

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