Acetic Acid → (2R)-2-[({6-[4-fluoro-3-(trifluoromethyl)phenyl]pyridin-2-yl}methyl)amino]-3-methylbutan-1-ol

HRID 1472924Notes

Reaction equation

HRID 1472924 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([CH:14]=O)[CH:11]=[CH:10][CH:9]=2)=[CH:4][C:3]=1[C:16]([F:19])([F:18])[F:17].[NH2:20][C@@H:21]([CH2:25][OH:26])[CH:22]([CH3:24])[CH3:23].C(O)(=O)C.C([BH3-])#N>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([CH2:14][NH:20][C@H:21]([CH:22]([CH3:24])[CH3:23])[CH2:25][OH:26])[CH:11]=[CH:10][CH:9]=2)=[CH:4][C:3]=1[C:16]([F:19])([F:18])[F:17]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 498716Cyano-borohydrideHCID 6950587D-ValinolHCID 848199696-(4-Fluoro-3-(trifluoromethyl)phenyl)picolinaldehyde

Product 1

HCID 68312365(2R)-2-[({6-[4-fluoro-3-(trifluoromethyl)phenyl]pyridin-2-yl}methyl)amino]-3-methylbutan-1-olYield 59%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of Example 267A (0.500 g, 1.86 mmol) in methanol (20 mL) at ambient temperature was added D-valinol (0.20 mL, 1.9 mmol) and acetic acid (0.40 mL, 7.4 mmol) followed by MP-cyanoborohydride (2.49 mmol/g; 1.0 g). After 2 hours, the mixture was filtered, concentrated and the residue partitioned between ether and 1M NaOH. The organic extract was concentrated and purified by chromatography to provide 390 mg (59%) of the title compound. MS (DCI+) m/z 270 (M+H); 1H NMR (500 MHz, CDCl3) δ 8.28 (dd, J=6.8, 2.0 Hz, 1H), 8.24-8.15 (m, 1H), 7.76 (t, J=7.7 Hz, 1H), 7.61 (d, J=7.8 Hz, 1H), 7.34-7.25 (m, 2H), 4.04 (q, J=14.5 Hz, 2H), 3.70 (dd, J=10.9, 4.0 Hz, 1H), 3.49 (dd, J=10.8, 6.9 Hz, 1H), 2.53 (td, J=6.7, 4.1 Hz, 1H), 1.97-1.85 (m, 1H), 1.04 (d, J=6.8 Hz, 3H), 0.97 (d, J=6.9 Hz, 3H).

Workup

  1. filtrationthe mixture was filtered
  2. concentrationconcentrated
  3. customthe residue partitioned between ether and 1M NaOH
  4. extractionThe organic extract
  5. concentrationwas concentrated
  6. custompurified by chromatography

Sources & evidence

ORD record
ord-d364635489bd4bcd967dadf304a741d0
Source dataset
uspto-grants-2015_04
Patent number
US09012651B2

Reaction notes

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