Hydrochloric Acid → HCID 57968790, compound

HRID 1471611Notes

Reaction equation

HRID 1471611 reaction equation
[NH2:1][CH2:2][C:3]1[CH:19]=[CH:18][C:6]([O:7][C:8]2[CH:17]=[CH:16][C:11]3[B:12]([OH:15])[O:13][CH2:14][C:10]=3[CH:9]=2)=[CH:5][CH:4]=1.[CH:20]1([CH:26]=O)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.[BH4-].[Na+].Cl>CCO>[CH:20]1([CH2:26][NH:1][CH2:2][C:3]2[CH:19]=[CH:18][C:6]([O:7][C:8]3[CH:17]=[CH:16][C:11]4[B:12]([OH:15])[O:13][CH2:14][C:10]=4[CH:9]=3)=[CH:5][CH:4]=2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 16275CyclohexanecarboxaldehydeHCID 4311764Sodium borohydrideHCID 57968923Crisaborole intermediate

Product 1

HCID 57968790HCID 57968790, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 5-(4-aminomethyl-phenoxy)-3H-benzo[c][1,2]oxaborol-1-ol (150 mg, 0.59 mmol, 1.0 eq.) in EtOH (5.0 mL) was added cyclohexanecarbaldehyde (280 μL, 2.36 mmol, 4.0 eq.). The mixture was stirred at room temperature for 30 minutes. After cooling to 0° C., NaBH4 (89 mg, 0.36 mmol, 4.0 eq.) was added in portions and the mixture was allowed to warm to room temperature and stirred for 2 h. The mixture was carefully treated with dilute HCl (5 mL) and aqueous phase was extracted with EtOAc (3×10 mL). Combined organic extracts was washed with brine (10 mL), dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. The residue was applied to silica chromatography eluting with MeOH/DCM (0:100 to 10:90) to give 5-{4-[(cyclohexylmethyl-amino)-methyl]-phenoxy}-3H-benzo[c][1,2]oxaborol-1-ol as a white solid. LCMS (m/z) 352 (M+H); 1H NMR (DMSO-d6) δ: 9.08 (s, 1H), 7.68 (d, J=8.0 Hz, 1H), 7.30-7.37 (m, J=8.5 Hz, 2H), 6.95-7.02 (m, 2H), 6.88-6.95 (m, 2H), 4.89 (s, 2H), 3.64 (s, 2H), 2.31 (d, J=6.6 Hz, 2H), 1.67-1.77 (m, 2H), 1.56-1.66 (m, 3H), 1.30-1.44 (m, 1H), 1.02-1.23 (m, 3H), 0.77-0.91 (m, 2H).

Workup

  1. temperatureAfter cooling to 0° C.
  2. temperatureto warm to room temperature
  3. stirringstirred for 2 h
  4. extractionwas extracted with EtOAc (3×10 mL)
  5. washCombined organic extracts was washed with brine (10 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. washeluting with MeOH/DCM (0:100 to 10:90)

Sources & evidence

ORD record
ord-b8a1cab6628f44f68469afac647ff6b8
Source dataset
uspto-grants-2015_04
Patent number
US09012431B2

Reaction notes

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