Borane → Trifluoroacetic acid

HRID 1889647Notes

Reaction equation

HRID 1889647 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:11]=[C:12]([CH:17]=[C:18]([O:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[CH:19]=2)[C:13](OC)=[O:14])=O)=[CH:4][CH:3]=1.B.[H-].[H-].[H-].[H-].[Li+].[Al+3].[C:37]([OH:43])([C:39]([F:42])([F:41])[F:40])=[O:38]>C1COCC1.CO.CCOC(C)=O>[F:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][NH:7][CH2:8][C:10]2[CH:11]=[C:12]([CH2:13][OH:14])[CH:17]=[C:18]([O:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[CH:19]=2)=[CH:4][CH:3]=1.[C:37]([OH:43])([C:39]([F:42])([F:41])[F:40])=[O:38]

Participants

9

Reactant 4

HCID 6331BoraneHCID 6422Trifluoroacetic acidHCID 21226445Aluminium lithium hydrideHCID 66616501HCID 66616501, compound

Product 2

HCID 6422Trifluoroacetic acidYield 54.6%HCID 66616484HCID 66616484, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl 3-(4-fluorobenzylcarbamoyl)-5-(4-fluorophenoxy)benzoate (2.7 g, 6.79 mmol) in 10 mL of THF at ice bath temp was added borane (40 mL of 1 M solution in THF) slowly. After 10 min, the mixture was warmed to rt, stirred for 30 min and heated at 50° C. for 10 h. The mixture was cooled to rt and treated with 10 mL of 1M solution of LiAlH4 in THF. The mixture was stirred for 2 h and treated with EtOAc. The resulting mixture was treated with MeOH and TFA slowly, stirred for a while, mostly concentrated. Water and MeOH were added to the residue and the insoluble material was filtered. The filtrate was concentrated. Purification of the residue using prep HPLC provided the desired product as a white solid of TFA salt (1.74 g, 54.6%). 1H NMR (CD3OD): δ 7.49˜6.97 (m, 11H), 4.56 (s, 2H), 4.19 (s, 2H), 4.16 (s, 2H); MS (ESI): (M+H)+=356.24.

Workup

  1. temperatureheated at 50° C. for 10 h
  2. temperatureThe mixture was cooled to rt
  3. stirringThe mixture was stirred for 2 h
  4. stirringstirred for a while
  5. concentrationmostly concentrated
  6. additionWater and MeOH were added to the residue
  7. filtrationthe insoluble material was filtered
  8. concentrationThe filtrate was concentrated
  9. customPurification of the residue

Sources & evidence

ORD record
ord-b8c6853f55a144bfa8c857e328372b40
Source dataset
uspto-grants-2013_08
Patent number
US08501992B2

Reaction notes

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