Triethylamine → N-((R)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-benzamide

HRID 1793052노트

반응식

HRID 1793052 반응식
[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[C:18]([F:19])=[C:17]([F:20])[CH:16]=[CH:15][C:11]=2[C:12]([OH:14])=O)=[C:5]([F:21])[CH:4]=1)[CH3:2].CC1(C)O[C@H](CNO)CO1.[CH3:32][C:33]1([CH3:42])[O:38][C@@H:37]([CH2:39][O:40][NH2:41])[CH2:36]C[O:34]1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>ClCCl>[CH3:42][C:33]1([CH3:32])[O:38][C@@H:37]([CH2:39][O:40][NH:41][C:12](=[O:14])[C:11]2[CH:15]=[CH:16][C:17]([F:20])=[C:18]([F:19])[C:10]=2[NH:9][C:6]2[CH:7]=[CH:8][C:3]([CH2:1][CH3:2])=[CH:4][C:5]=2[F:21])[CH2:36][O:34]1

참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 2724699PyBOPHCID 220256532-[(4-Ethyl-2-fluorophenyl)amino]-3,4-difluorobenzoic acidHCID 23541087(S)-(+)-2,2-Dimethyl-4-hydroxyaminomethyl-1,3-dioxolaneHCID 69628065(R)-O-(2,2-dimethyl-[1,3]dioxan-4-ylmethyl)-hydroxylamine

생성물 1

HCID 86590726N-((R)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-benzamide

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a stirring solution of the product of Example 1, Step D, 2-[(4-ethyl-2-fluorophenyl)amino]-3,4-difluorobenzoic acid (0.480 g, 1.626 mmol) in dichloromethane (25 mL) is added to the product of Example 31, Step D, (R)—O-(2,2-dimethyl-[1,3]dioxan-4-ylmethyl)-hydroxylamine (0.38 g, 2.57 mmol), triethylamine (0.54 mL, 3.85 mmol), and benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate (1.34 g, 2.57 mmol) and allowed to stir at ambient temperature for 90 minutes. The reaction mixture was concentrated in vacuo and the affording residue was partitioned between ethyl acetate and water. The organic layers were washed twice with saturated sodium carbonate solution and twice with brine. The organic layer was collected, dried over sodium sulfate, filtered and concentrated in vacuo. N-((R)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-benzamide was isolated via silica column chromatography in 4:1 hexanes/ethyl acetate, then 3:1 hexanes/ethyl acetate affording a white foam (0.515 g, 56.7%).

후처리

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe affording residue was partitioned between ethyl acetate and water
  3. washThe organic layers were washed twice with saturated sodium carbonate solution and twice with brine
  4. customThe organic layer was collected
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-8f5b4bb3d9eb4f009cf884288ecb6d46
출처 데이터셋
uspto-grants-2006_07
특허 번호
US07078438B2

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