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Potassium Hydroxide → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(2'-chloro-4-cyclopropyl-5'-isopropylbiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

HRID 1994642
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HRID 1994642 반응식
[F:1][C:2]([F:39])([F:38])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24](Br)[CH:23]=[CH:22][C:21]=3[C:27]3[CH:32]=[C:31]([CH:33]([CH3:35])[CH3:34])[CH:30]=[CH:29][C:28]=3[Cl:36])[C@H:14]2[CH3:37])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH:40]1(B(O)O)[CH2:42][CH2:41]1.[OH-].[K+]>O1CCOCC1.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:1][C:2]([F:39])([F:38])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([CH:40]4[CH2:42][CH2:41]4)[CH:23]=[CH:22][C:21]=3[C:27]3[CH:32]=[C:31]([CH:33]([CH3:35])[CH3:34])[CH:30]=[CH:29][C:28]=3[Cl:36])[C@H:14]2[CH3:37])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 3

HCID 14797Potassium HydroxideHCID 2760897Cyclopropylboronic acidHCID 11556418(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(4-bromo-2'-chloro-5'-isopropylbiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

생성물 1

HCID 11527223(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(2'-chloro-4-cyclopropyl-5'-isopropylbiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

시약·촉매·용매 2

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
촉매
HCID 312751,4-Dioxane용매

실험 절차

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(4-bromo-2′-chloro-5′-isopropylbiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one (27 mg, 0.043 mmol) in 1,4-dioxane (1 mL) was added cyclopropylboronic acid (9 mg, 0.10 mmol), [1,1′-bis(diphenylphosphino) ferrocene] dichloropalladium (II) (10.4 mg, 30 mol %) and aqueous potassium hydroxide (42 μL, 3M, 3 eq.). The reaction mixture was purged with nitrogen and then sealed in a microwave vessel. The reaction vessel was subject to microwave irradiation at 120° C. for 20 min. Crude mixture was worked up with water and EtOAc. The combined organic extracts were dried over Na2SO4 and concentrated in vacuo to give the crude product. This was purified by preparative TLC plate eluted by 20% EtOAc in hexanes to afford the titled compound. LC-MS: 595.99 (M+1)+. 1H NMR (CDCl3, 500 MHz) a 6:4 mixture of rotamers δ 7.82-7.86 (m, 1H), 7.66-7.72 (m, 2H), 7.36-7.40 (m, 1H), 7.21-7.23 (m, 0.5H), 7.11-7.19 (m, 3H), 7.01-7.08 (m, 1.5H), 5.58 (d, J=8.0 Hz, 0.4H), 5.50 (d, J=8.0 Hz, 0.6H), 4.88 (d, J=15.1 Hz, 0.6H), 4.71 (d, J=15.6 Hz, 0.4H), 3.76-3.95 (m, 2H), 2.84-2.95 (m, 1H), 1.92-2.00 (m, 1H), 1.18-1.29 (m, 6H), 1.00-1.07 (m, 2H), 0.71-0.82 (m, 2H), 0.47 (d, J=6.6 Hz, 1.2H), 0.42 (d, J=6.6 Hz, 1.8H).

후처리

  1. customThe reaction mixture was purged with nitrogen
  2. customsealed in a microwave vessel
  3. customirradiation at 120° C. for 20 min
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customto give the crude product
  7. customThis was purified by preparative TLC plate
  8. washeluted by 20% EtOAc in hexanes

출처 및 근거

ORD 기록
ord-ce3961a811bc4e8581ea115844d0e18a
출처 데이터셋
uspto-grants-2010_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07652049B2

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