HCID 90418967, compound → HCID 90418922, compound

HRID 2202388Notes

Reaction equation

HRID 2202388 reaction equation
[F:1][CH:2]([F:19])[C:3]#[C:4][C:5]1([OH:18])[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1>C1COCC1>[F:19][CH:2]([F:1])/[CH:3]=[CH:4]/[C:5]1([OH:18])[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])[CH2:7][CH2:6]1

Participants

3

Reactant 1

HCID 90418967HCID 90418967, compound

Product 1

HCID 90418922HCID 90418922, compoundYield 103.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of tert-butyl 4-(3,3-difluoroprop-1-yn-1-yl)-4-hydroxypiperidine-1-carboxylate (280 mg, 1.016 mmol) in 30 mL of anhydrous THF was added dropwise sodium dihydro-bis-(2-methoxyethoxy)aluminate (587 mg, 2.032 mmol, 70%) at −78° C. under N2. After the addition, the reaction mixture was stirred at −78° C. under N2 for 5 h. The reaction mixture was quenched by sat. NH4Cl aq., and the resulting mixture was extracted with EtOAc (50 mL, 30 mL). The combined organic phase was washed with brine, dried over anhy. Na2SO4 and concentrated in vacuo to afford 291 mg of title compound. MS (ES) M+H expected 278.15. found 178.30. 1H NMR (CHLOROFORM-d) δ: 6.29-6.08 (m, 2H), 6.01-5.84 (m, 1H), 3.98-3.84 (m, 2H), 3.20 (t, J=11.4 Hz, 2H), 1.76-1.62 (m, 4H), 1.48 (s, 9H).

Workup

  1. additionAfter the addition
  2. customThe reaction mixture was quenched by sat. NH4Cl aq.
  3. extractionthe resulting mixture was extracted with EtOAc (50 mL, 30 mL)
  4. washThe combined organic phase was washed with brine
  5. customdried over anhy
  6. concentrationNa2SO4 and concentrated in vacuo

Sources & evidence

ORD record
ord-4ac6a048a6334135b1ca6d06f6a682c2
Source dataset
uspto-grants-2016_06
Patent number
US09365545B2

Reaction notes

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