Trimethyl borate → HCID 57936245, 화합물

HRID 1434909노트

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HRID 1434909 반응식
[CH3:1][C:2]([OH:11])([CH2:4][CH2:5][C:6]1[S:7][CH:8]=[CH:9][CH:10]=1)[CH3:3].[Li+].CC([N-]C(C)C)C.COB(OC)OC.[Cl:27][C:28]1[N:33]=[C:32](Cl)[CH:31]=[CH:30][N:29]=1.C(=O)(O)[O-].[Na+]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC>[Cl:27][C:28]1[N:33]=[C:32]([C:8]2[S:7][C:6]([CH2:5][CH2:4][C:2]([CH3:1])([OH:11])[CH3:3])=[CH:10][CH:9]=2)[CH:31]=[CH:30][N:29]=1

참가 물질

9

반응물 5

HCID 8470Trimethyl borateHCID 775312,4-DichloropyrimidineHCID 516892Sodium BicarbonateHCID 2724682Lithium diisopropylamideHCID 326398272-Methyl-4-(thiophen-2-yl)butan-2-ol

생성물 1

HCID 57936245HCID 57936245, 화합물

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매HCID 80711,2-Dimethoxyethane용매2회

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온도
100 °C

실험 절차

A solution of 2-methyl-4-thiophen-2-yl-butan-2-ol (630 mg, 3.7 mmol) in 10 ml of THF was treated with LDA (4.6 ml of 2M solution in THF/heptane/ethylbenzene, 9.2 mmol) at −78° C. under nitrogen and the mixture was stirred for 5 minutes. Then, trimethylborate (1 ml, 9.2 mmol) was added in one portion and the cooling bath was removed. After 15 minutes, the mixture was quenched with 50 ml of saturated ammonium chloride solution and extracted twice with EtOAc. The combined organic extracts were washed with brine and evaporated under reduced pressure at room temperature. This crude boronic acid was redissolved in 10 ml of DME and added to a stirred suspension 2,4-dichloro-pyrimidine (275 mg, 1.85 mmol), Pd(PPh3)4 (64 mg, 0.037 mmol), 20 ml of DME and 5 ml of a 10% solution of sodium bicarbonate. This mixture was then kept at reflux (100° C. heat bath) for 90 minutes. After cooling, most of the DME was evaporated and the crude was partitioned between water and EtOAc. The organic layer was separated, washed with 0.2N-HCl, water and brine, dried over sodium sulfate and evaporated. The crude was purified by chromatography on silicagel (EtOAc/hexane:1/1). Yield: 390 mg (77%) of 4-[5-(2-Chloro-pyrimidin-4-yl)-thiophen-2-yl]-2-methyl-butan-2-ol.

후처리

  1. customthe cooling bath was removed
  2. waitAfter 15 minutes
  3. customthe mixture was quenched with 50 ml of saturated ammonium chloride solution
  4. extractionextracted twice with EtOAc
  5. washThe combined organic extracts were washed with brine
  6. customevaporated under reduced pressure at room temperature
  7. dissolutionThis crude boronic acid was redissolved in 10 ml of DME
  8. temperatureat reflux
  9. customwas evaporated
  10. customthe crude was partitioned between water and EtOAc
  11. customThe organic layer was separated
  12. washwashed with 0.2N-HCl, water and brine
  13. dry with materialdried over sodium sulfate
  14. customevaporated
  15. customThe crude was purified by chromatography on silicagel (EtOAc/hexane:1/1)

출처 및 근거

ORD 기록
ord-6859600279de44cc8e58026d9da4f290
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07615562B2

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