HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

Methanol → Crisaborole intermediate

HRID 1255762
Notes
Print preview

Reaction equation

HRID 1255762 reaction equation
[OH:1][B:2]1[C:6]2[CH:7]=[CH:8][C:9]([O:11][C:12]3[CH:20]=[CH:19][C:15]([C:16](O)=[O:17])=[CH:14][CH:13]=3)=[CH:10][C:5]=2[CH2:4][O:3]1.B(OC)(OC)OC.CO.C([O-])(O)=O.[Na+]>C1COCC1.CCOC(C)=O>[OH:17][CH2:16][C:15]1[CH:19]=[CH:20][C:12]([O:11][C:9]2[CH:8]=[CH:7][C:6]3[B:2]([OH:1])[O:3][CH2:4][C:5]=3[CH:10]=2)=[CH:13][CH:14]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 887MethanolHCID 8470Trimethyl borateHCID 516892Sodium BicarbonateHCID 25010450Benzoic acid, 4-[(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-5-yl)oxy]-

Product 1

HCID 57969145Crisaborole intermediate

Reagents, catalysts & solvents 2

HCID 8028
Tetrahydrofuran
Solvent
2×
HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(1-hydroxy-1,3-dihydro-benzo[c][1,2]oxaborol-5-yloxy)-benzoic acid (200 mg, 0.74 mmol, 1.0 eq.), trimethyl borate (0.5 mL, 4.4 mmol, 6.0 eq.) in THF (7.0 mL) was added borane tetrahydrofuran complex solution (1.5 mL, 1.0 M in THF, 1.5 mmol, 2.0 eq.) dropwise under nitrogen atmosphere. The mixture was stirred at room temperature overnight. The mixture was carefully treated with MeOH (2 mL) and poured into EtOAc (10 mL) and sat. NaHCO3 (10 mL). The layers were separated and the 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-hydroxymethyl-phenoxy)-3H-benzo[c][1,2]oxaborol-1-ol as a white solid. LCMS (m/z) 279 (M+23); 1H NMR (DMSO-d6) δ: 9.09 (s, 1H), 7.70 (d, J=8.0 Hz, 1H), 7.34-7.38 (m, J=8.7 Hz, 2H), 7.01-7.05 (m, 2H), 6.96 (dd, J=8.0, 2.1 Hz, 1H), 6.91-6.93 (m, 1H), 5.18 (t, J=5.7 Hz, 1H), 4.91 (s, 2H), 4.49 (d, J=5.7 Hz, 2H).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous phase was extracted with EtOAc (3×10 mL)
  3. washCombined organic extracts was washed with brine (10 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. washeluting with MeOH/DCM (0:100 to 10:90)

Sources & evidence

ORD record
ord-7360cc07da7d4df9980a7106e0ccebd9
Source dataset
uspto-grants-2013_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08461135B2

Reaction notes

Loading…

On this pageParticipantsProcedureWorkupSources & evidenceReaction notes