Diethyl Ether → HCID 86697745, compound

HRID 2279804Notes

Reaction equation

HRID 2279804 reaction equation
CCOCC.Cl[C:7]1[N:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[C:9]([Cl:17])[N:8]=1.[NH2:18][C:19]1[CH:33]=[CH:32][C:22]([CH2:23][P:24](=[O:31])([O:28][CH2:29][CH3:30])[O:25][CH2:26][CH3:27])=[CH:21][C:20]=1[Br:34].C(N(C(C)C)CC)(C)C>ClC(Cl)C.C(O)(C)(C)C.[Cl-].[Zn+2].[Cl-]>[Br:34][C:20]1[CH:21]=[C:22]([CH:32]=[CH:33][C:19]=1[NH:18][C:7]1[N:8]=[C:9]([Cl:17])[C:10]([C:13]([F:16])([F:15])[F:14])=[CH:11][N:12]=1)[CH2:23][P:24](=[O:31])([O:28][CH2:29][CH3:30])[O:25][CH2:26][CH3:27]

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 81531DiisopropylethylamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 86654008Phosphonic acid, P-[(4-amino-3-bromophenyl)methyl]-, diethyl ester2×

Product 1

HCID 86697745HCID 86697745, compoundYield 23%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 63651,1-DichloroethaneSolvent2×HCID 6386tert-ButanolSolvent2×

Procedure

A 1M solution of zinc chloride in ether (18.7 mL, 18.7 mmol) was added to a solution of 2,6-dichloro-5-trifluoromethylpyrimidine (4 g, 18.72 mmol) in 20 mL of dichloroethane and t-butanol (1:1) under nitrogen atmosphere. The reaction mixture was stirred at rt for 30 min, cooled to 0° C. and then treated slowly over 10 min with a solution of diethyl (4-amino-3-bromobenzyl)phosphonate (Compound 32D, 3.35 gm, 10.4 mmol) in dichloroethane and t-butanol (10 mL, 1:1) through an addition funnel and stirred for 1 hr. Diisopropylethylamine (3.2 mL, 10.4 mmol) was added and the mixture was allowed to stir at rt for 3 days. The solvents were evaporated and the residue was purified using flash column chromatography (0-30% EtOAc/DCM) to afford 1.2 g of the title compound (23%). 1H NMR (400 MHz, CDCl3): δ 1.23-1.25 (m, 6H), 3.10 (d, J=22.0 Hz, 2H), 3.99-4.06 (m, 4H), 7.28 (d, J=8.4 Hz, 1H), 7.52 (s, 1H), 7.8 (s, 1H), 8.26 (d, J=8.4 Hz, 1H), 8.57 (s, 1H).

Workup

  1. temperaturecooled to 0° C.
  2. stirringstirred for 1 hr
  3. stirringto stir at rt for 3 days
  4. customThe solvents were evaporated
  5. customthe residue was purified

Sources & evidence

ORD record
ord-04aff6e4b6cc4d888f6b00668136ecbc
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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