Acetic Acid → (+/-)-(2R,3R)-1-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-[(3-chloro-4-cyano-2-methylphenylamino)-methyl]piperidine

HRID 751162

反応式

HRID 751162 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[C@H:9]1[CH:22]=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:24][C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[C:27]([Cl:33])[C:26]=1[CH3:34].CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:16])[CH3:17])[C@H:9]1[CH2:22][NH:24][C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[C:27]([Cl:33])[C:26]=1[CH3:34])=[O:7])([CH3:2])([CH3:3])[CH3:4]

参加物

6

反応物 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydride2 回HCID 218754134-Amino-2-chloro-3-methylbenzonitrileHCID 86594307(+/-)-(2S,3R)-1-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-formylpiperidine

生成物 1

HCID 59754257(+/-)-(2R,3R)-1-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-[(3-chloro-4-cyano-2-methylphenylamino)-methyl]piperidine収率 20.2%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

実験手順

A mixture of 77F (660 mg, 1.92 mmol), 4-amino-2-chloro-3-methylbenzonitrile (384 mg, 2.3 mmol, 1.2 equiv) and HOAc (165 μL, 2.88 mmol, 1.5 equiv) in 1,2-DCE (10 mL) was stirred at rt for 30 min and Na(OAc)3BH (610 mg, 2.88 mmol, 1.5 equiv) was added. The reaction was stirred at rt overnight. Another 407 mg of Na(OAc)3BH (610 mg, 1.92 mmol, 1.0 equiv) was added and stirred at rt for another 24 h. The mixture was concentrated and the residue was diluted with EtOAc (30 mL), washed with saturated sodium bicarbonate solution (2×15 mL), brine (2×15 mL), dried (MgSO4) and evaporated to give the crude product. Purification of the crude product by flash chromatography (0-50% EtOAc/hexane) yield the desired product 77G (192 mg, 20%) as a white foam: Rf (30% EtOAc/hexane) 0.37; HPLC (Phenomenex Luna 5μ C18 4.6×50 mm, linear gradient over 4 min) retention time 4.6 min (100%); MS (ES) m/z 344.1 [M+1]+; HRMS calcd for C25H41N3O3SiCl 494.2606, Found 494.2613.

後処理

  1. stirringThe reaction was stirred at rt overnight
  2. stirringstirred at rt for another 24 h
  3. concentrationThe mixture was concentrated
  4. additionthe residue was diluted with EtOAc (30 mL)
  5. washwashed with saturated sodium bicarbonate solution (2×15 mL), brine (2×15 mL)
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customto give the crude product
  9. customPurification of the crude product by flash chromatography (0-50% EtOAc/hexane)

出典と根拠

ORDレコード
ord-affa58f2c4c440f183c8e2f141815233
出典データセット
uspto-grants-2008_07
特許番号
US07405234B2

関連ノート

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