Triethylamine → [Bis-(4-methoxy-phenyl)-phenyl-methyl]-((R)-4-(6-bromo-3-fluoro-pyridin-2-yl)-5,5-difluoro-4,6,6-trimethyl-5,6-dihydro-4H-[1,3]oxazin-2-yl)-amine

HRID 1752462Notes

Reaction equation

HRID 1752462 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C@:8]2([CH3:19])[C:13]([F:15])([F:14])[C:12]([CH3:17])([CH3:16])[O:11][C:10]([NH2:18])=[N:9]2)[C:5]([F:20])=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:28][O:29][C:30]1[CH:51]=[CH:50][C:33]([C:34](Cl)([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)=[CH:32][CH:31]=1>ClCCl>[CH3:42][O:41][C:38]1[CH:37]=[CH:36][C:35]([C:34]([NH:18][C:10]2[O:11][C:12]([CH3:16])([CH3:17])[C:13]([F:14])([F:15])[C@:8]([C:6]3[C:5]([F:20])=[CH:4][CH:3]=[C:2]([Br:1])[N:7]=3)([CH3:19])[N:9]=2)([C:33]2[CH:32]=[CH:31][C:30]([O:29][CH3:28])=[CH:51][CH:50]=2)[C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[CH:40][CH:39]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 968311,1'-(Chlorophenylmethylene)bis(4-methoxybenzene)HCID 86689146(R)-4-(6-Bromo-3-fluoro-pyridin-2-yl)-5,5-difluoro-4,6,6-trimethyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine

Product 1

HCID 86689147[Bis-(4-methoxy-phenyl)-phenyl-methyl]-((R)-4-(6-bromo-3-fluoro-pyridin-2-yl)-5,5-difluoro-4,6,6-trimethyl-5,6-dihydro-4H-[1,3]oxazin-2-yl)-amineYield 102.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-4-(6-bromo-3-fluoro-pyridin-2-yl)-5,5-difluoro-4,6,6-trimethyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (106 mg, 0.301 mmol) and triethylamine (60.9 mg, 0.602 mmol) in dichloromethane (3 ml) was added solid 4,4′-dimethoxytrityl chloride (112 mg, 0.331 mmol) under argon atmosphere. The green solution was stirred at rt for 2 hrs and was then evaporated in vacuo. The crude product was taken up with ethyl acetate and washed with aqueous sodium bicarbonate solution, water and brine. The organic phase was dried over sodium sulfate, filtered and evaporated. Filtration over silica gel (4.4 g, toluene/ethyl acetate 6:4) afforded the title compound as a blue-gray foam (202 mg, 96%).

Workup

  1. customwas then evaporated in vacuo
  2. washwashed with aqueous sodium bicarbonate solution, water and brine
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. filtrationFiltration over silica gel (4.4 g, toluene/ethyl acetate 6:4)

Sources & evidence

ORD record
ord-5945784eba7f49e99ca3410b949990b5
Source dataset
uspto-grants-2015_10
Patent number
US09163011B2

Reaction notes

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