Acetic Acid → HCID 90406811, compound

HRID 2277066Notes

Reaction equation

HRID 2277066 reaction equation
CC(O)=O.[O:5]1[CH2:10][CH2:9][CH:8]([CH:11]=O)[CH2:7][CH2:6]1.[NH2:13][C:14]1[CH:15]=[C:16]([C@H:20]([OH:24])[CH2:21][C:22]#[N:23])[CH:17]=[CH:18][CH:19]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.C([O-])(O)=O.[Na+]>[OH:24][C@@H:20]([C:16]1[CH:17]=[CH:18][CH:19]=[C:14]([NH:13][CH2:11][CH:8]2[CH2:7][CH2:6][O:5][CH2:10][CH2:9]2)[CH:15]=1)[CH2:21][C:22]#[N:23]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 9964078Tetrahydro-2H-pyran-4-carboxaldehydeHCID 90406445HCID 90406445, compound

Product 1

HCID 90406811HCID 90406811, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

CH3COOH (1 mL) was added to a solution of tetrahydro-2H-pyran-4-carbaldehyde (0.7 g, 6.12 mmol) and (R)-3-(3-aminophenyl)-3-hydroxypropanenitrile (1.0 g, 6.12 mmol) in CH2Cl2 (20 mL) at 0° C. followed by the addition of Na(OAc)3BH (3.89 g, 18.34 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with NaHCO3 (50 mL), extracted with EtOAc (200 mL), organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography (50% EtOAc: hexanes) gave (R)-3-hydroxy-3-(3-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)propanenitrile as a pale yellow liquid. Yield (1.0 g, 63%); 1H NMR (400 MHz, DMSO-d6) δ 7.02 (t, J=8.0 Hz, 1H), 6.62 (s, 1H), 6.51 (d, J=7.2 Hz, 1H), 6.47 (d, J=7.6 Hz, 1H), 5.77 (d, J=4.4 Hz, 1H), 5.68 (t, J=5.2 Hz, 1H), 4.73 (dd, J=10.8, 4.8 Hz, 1H), 3.85 (dd, J=10.8, 2.8 Hz, 2H), 3.26 (t, J=11.2 Hz, 2H), 2.89 (t, J=6.0 Hz, 2H), 2.82 (dd, J=16.8, 4.8 Hz, 1H), 2.73 (dd, J=16.8, 6.8 Hz, 1H), 1.81-1.75 (m, 1H), 1.66 (d, J=12.8 Hz, 2H), 1.23-1.19 (m, 2H).

Workup

  1. extractionextracted with EtOAc (200 mL), organic layer
  2. dry with materialwas dried over anhydrous Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customPurification by flash chromatography (50% EtOAc: hexanes)

Sources & evidence

ORD record
ord-56376134f9b844bca715fe19f4c2b777
Source dataset
uspto-grants-2015_09
Patent number
US09133154B2

Reaction notes

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