Ethyl Acrylate → tert-butyl (3RS,4RS)-4-[4-(2-ethoxycarbonyl-vinyl)-phenyl]-3-hydroxy-piperidine-1-carboxylate

HRID 1004992

反応式

HRID 1004992 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH:9]2[OH:21])=[CH:4][CH:3]=1.[C:22]([O:26][CH2:27][CH3:28])(=[O:25])[CH:23]=[CH2:24].C([O-])(=O)C.[Na+]>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>[CH2:27]([O:26][C:22]([CH:23]=[CH:24][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH:9]2[OH:21])=[CH:4][CH:3]=1)=[O:25])[CH3:28]

参加物

7

反応物 3

HCID 8821Ethyl AcrylateHCID 517045Sodium AcetateHCID 54537313tert-butyl (3RS,4RS)-4-(4-bromophenyl)-3-hydroxy-piperidine-1-carboxylate

生成物 1

HCID 86604399tert-butyl (3RS,4RS)-4-[4-(2-ethoxycarbonyl-vinyl)-phenyl]-3-hydroxy-piperidine-1-carboxylate収率 77.5%

試薬・触媒・溶媒 3

HCID 80271Tri-o-tolylphosphine触媒2 回HCID 167845palladium(II) acetate触媒2 回HCID 6228Dimethylformamide溶媒3 回

実験手順

A Schlenk tube was charged under argon with 25.6 mg (0.114 mmol) of Pd(OAc)2, 69.6 mg (0.Z29 mmol) of tri(o-tolyl)phosphine and 20 ml of DMF (distilled under argon) and the reaction mixture was stirred at room temperature for 1 5 minutes. A 200 ml sulphonation flask was charged under argon and while stirring with 8.15 g (22.9 mmol) of tert-butyl (3RS,4RS)-4-(4-bromo-phenyl)-3-hydroxy-piperidine-1-carboxylate [Example 25 (c)], 100 ml of DMF, 3.73 ml (34.3 mmol) of ethyl acrylate, 2.25 g (27.5 mmol) of sodium acetate and the yellow catalyst solution. The reaction mixture was stirred at 120° C. for 6 hours. In order to complete the reaction, a solution of 5.1 mg Pd(OAc)2 and 14.3 mg of tri(o-tolyl)phosphine in 5 ml of DMF was added after 5 hours. The dark reaction mixture was evaporated on a rotary evaporator. The grey solid residue was taken up in ether and the turbid solution was washed three times with water, dried over sodium sulphate and evaporated under reduced pressure. The yellow solid residue was chromatographed on 250 g of silica gel using a 2:1 mixture of hexane and ethyl acetate as the eluent. After crystallization from ethyl acetate there were obtained 6.66 g (77% of theory) of tert-butyl (3RS,4RS)-4-[4-(2-ethoxycarbonyl-vinyl)-phenyl]-3-hydroxy-piperidine-1-carboxylate as colourless crystals; MS: 376 (M+H)+.

後処理

  1. additionA 200 ml sulphonation flask was charged under argon
  2. stirringThe reaction mixture was stirred at 120° C. for 6 hours
  3. customthe reaction
  4. customThe dark reaction mixture
  5. customwas evaporated on a rotary evaporator
  6. washthe turbid solution was washed three times with water
  7. dry with materialdried over sodium sulphate
  8. customevaporated under reduced pressure
  9. customThe yellow solid residue was chromatographed on 250 g of silica gel using
  10. additiona 2:1 mixture of hexane and ethyl acetate as the eluent
  11. customAfter crystallization from ethyl acetate

出典と根拠

ORDレコード
ord-e84ca2e1e50445ec9ae75d455ce7f9eb
出典データセット
uspto-grants-2000_04
特許番号
US06051712

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