Sodium Hydroxide → HCID 71522264, compound

HRID 1621005Notes

Reaction equation

HRID 1621005 reaction equation
[OH:1][C@H:2]([C:9]1([C:13]2[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=2)[CH2:12][CH2:11][CH2:10]1)[C@H:3]1[CH2:7][CH2:6][CH2:5][C:4]1=O.C([O-])(=O)C.[Na+].Cl.NO.C([O-])(=O)C.[NH4+].C([BH3-])#[N:38].[Na+].[OH-].[Na+]>[Cl-].[Ti+3].[Cl-].[Cl-].CO>[NH2:38][C@H:4]1[CH2:5][CH2:6][CH2:7][C@@H:3]1[C@@H:2]([C:9]1([C:13]2[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=2)[CH2:12][CH2:11][CH2:10]1)[OH:1]

Participants

9

Reactant 6

HCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 89572961HCID 89572961, compound

Product 1

HCID 71522264HCID 71522264, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 10313229titanium(III) trichlorideCatalystHCID 887MethanolSolvent

Procedure

The mixture of Example 222A (285 mg, 0.868 mmol), methanol (5 mL), sodium acetate (85 mg, 1.042 mmol) and hydroxylamine hydrochloride (72.4 mg, 1.042 mmol) was heated in a 50° C. oil bath. After 15 minutes, the reaction mixture was cooled to room temperature and added ammonium acetate (736 mg, 9.55 mmol), sodium cyanoborohydride (164 mg, 2.60 mmol), and titanium(III)chloride (2.414 mL, 1.910 mmol) (dropwise to keep the internal temperature at about 35° C.). After 10 minutes, 2N NaOH was added and the mixture was extracted with EtOAc. The organic phase was dried (Na2SO4), filtered, and concentrated. Purification of the residue using a Waters C8 OBD SunFire 30 mm×75 mm eluted with acetonitrile/0.1% TFA afforded Example 222B as a trifluoroacetate salt in 34% yield. MS (ESI+) M/Z 330 (M+H). 1H NMR (500 MHz, CD3OD) δ ppm 7.47-7.49 (m, 2H), 7.21-7.23 (m, 2H), 3.87 (d, J=9.5 Hz, 1H), 3.35 (q, J=8.4 Hz, 1H), 2.51-2.58 (m, 1H), 2.39-2.47 (m, 1H), 2.32-2.39 (m, 1H), 2.24-2.32 (m, 1H), 1.90-2.05 (m, 2H), 1.76-1.85 (m, 1H), 1.57-1.76 (m, 3H), 1.25-1.45 (m, 3H).

Workup

  1. customat about 35° C.
  2. waitAfter 10 minutes
  3. extractionthe mixture was extracted with EtOAc
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the residue
  8. washeluted with acetonitrile/0.1% TFA

Sources & evidence

ORD record
ord-93569b4a68bd45d4b38a7be390721e4e
Source dataset
uspto-grants-2014_07
Patent number
US08772500B2

Reaction notes

Loading…