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Triethylamine → Methyl 4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzoate

HRID 354308
ノート
印刷プレビュー

反応式

HRID 354308 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[C:4]([F:22])[CH:3]=1.CCN(CC)CC.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CS(C)=O.CO.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:18]([O:17][C:15]([N:11]1[CH2:12][CH2:13][CH2:14][CH:10]1[CH2:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([C:15]([O:17][CH3:18])=[O:16])=[CH:3][C:4]=1[F:22])=[O:16])([CH3:21])([CH3:20])[CH3:19]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 235119311-Bromo-4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzene

生成物 1

HCID 23512180Methyl 4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzoate収率 124.5%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate
触媒
HCID 679Dimethyl Sulfoxide溶媒
HCID 887Methanol溶媒

反応条件

温度
70 °C

実験手順

To a stirred solution of 1-bromo-4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzene (549.4 mg, 1.468 mmol) in DMSO (6 mL) and MeOH (5 mL) was added Et3N (448 ul, 3.229 mmol), Pd(OAc)2 (36.2 mg, 0.161 mmol), and 1,3-bis(diphenylphosphino)propane (66.4 mg, 0.161 mmol). To the mixture was induced CO gas for 10 min. The resulting mixture was stirred at 70° C. for 2 days under a current of CO. After the mixture was concentrated, the residue was diluted with EtOAc. The solution was washed with brine and dried over Na2SO4. The solvent was removed under a reduced pressure and the residue was chromatographed on silica-gel eluting with n-hexane:EtOAc (5:1, v/v) as eluent to afford 323.0 mg (62%) methyl 4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzoate as a pale yellow oil. 1H-NMR (400 m/z, CDCl3) δ1.47 (s, 9H), 1.87(br s, 1H), 1.95-2.10 (m, 3H), 3.34-3.44 (br m, 2), 3.89 (s,. 3H), 3.94 and 4.11-4.26 (br m each, 3H), 7.03-7.11 (m, 1H), 7.75-7.80 (m, 2H); MS (FAB) m/z 354 (M++1).

後処理

  1. customfor 10 min
  2. concentrationAfter the mixture was concentrated
  3. additionthe residue was diluted with EtOAc
  4. washThe solution was washed with brine
  5. dry with materialdried over Na2SO4
  6. customThe solvent was removed under a reduced pressure
  7. customthe residue was chromatographed on silica-gel
  8. washeluting with n-hexane:EtOAc (5:1

出典と根拠

ORDレコード
ord-f0645b80915d450e83f26a20643e798e
出典データセット
uspto-grants-2004_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06756378B2

反応ノート

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