Allylamine → 1-Allyl-5-benzyloxy-2-difluoromethyl-1H-pyridin-4-one

HRID 1187453Notes

Reaction equation

HRID 1187453 reaction equation
[CH2:1]([O:8][C:9]1[C:10](=[O:18])[CH:11]=[C:12]([CH:15]([F:17])[F:16])O[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:19]([NH2:22])[CH:20]=[CH2:21]>CO>[CH2:19]([N:22]1[CH:14]=[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:10](=[O:18])[CH:11]=[C:12]1[CH:15]([F:16])[F:17])[CH:20]=[CH2:21]

Participants

4

Reactant 2

HCID 7853AllylamineHCID 598182925-Benzyloxy-2-difluoromethyl-pyran-4-one

Product 1

HCID 672815961-Allyl-5-benzyloxy-2-difluoromethyl-1H-pyridin-4-oneYield 73.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 5-benzyloxy-2-difluoromethyl-pyran-4-one (4.00 g, 15.8 mmol), allylamine (3.60 mL, 47.5 mmol) in methanol (40 mL) was stirred at room temperature for 1 hour. The reaction mixture was evaporated to dryness, and the residual solid was dissolved in 10 mL of ethyl acetate, and again concentrated in vacuo. The solid was suspended in a mixture of ethyl acetate and ether, then collected by suction filtration and thoroughly washed with ether. The off-white solid was dried to constant weight in a vacuum oven at 40° C. to afford the title product (3.38 g, 73% yield). HPLC purity (peak area percent) is 98.9% at λ=278 nm using HPLC Method 1 as described above. 1H NMR (400 MHz, CDCl3) δ (ppm): 7.35-7.43 (m, 5H, ArH), 7.16 (s, 1H), 6.79 (s, 1H), 6.48 (t, J=53.1 Hz, 1H, CF2H), 5.80-5.86 (m, 1H), 5.29 (d, J=10.4 Hz, 1H), 5.22 (s, 2H, OCH2), 5.10 (d, J=17.1 Hz, 1H), 4.58 (d, J=5.2 Hz, 2H); MS-ESI (m/z): 291.9 [M+1]+, 91.0.

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. dissolutionthe residual solid was dissolved in 10 mL of ethyl acetate
  3. concentrationagain concentrated in vacuo
  4. additionThe solid was suspended in a mixture of ethyl acetate and ether
  5. filtrationcollected by suction filtration
  6. washthoroughly washed with ether
  7. customThe off-white solid was dried to constant weight in a vacuum oven at 40° C.

Sources & evidence

ORD record
ord-892c1fc10de04841b2cb9e1fa5b82b77
Source dataset
uspto-grants-2014_03
Patent number
US08673943B2

Reaction notes

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