Methylamine → HCID 66872875、化合物

HRID 1470276ノート

反応式

HRID 1470276 の反応式
[CH3:1][NH2:2].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C:13]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)([CH:16]=O)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[BH4-].[Na+]>C(O)C>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C:13]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)([CH2:16][NH:2][CH3:1])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]

参加物

5

反応物 3

HCID 6329MethylamineHCID 4311764Sodium borohydrideHCID 59840466Tert-butyl 4-(4-chlorophenyl)-4-formylpiperidine-1-carboxylate

生成物 1

HCID 66872875HCID 66872875、化合物収率 68%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

A mixture of methylamine in ethanol (18 ml, 33% in ethanol) and 4-(4-chlorophenyl)-4-formyl-piperidine-1-carboxylic acid tert-butyl ester (206 mg, 0.62 mmol) was stirred at room temperature overnight. The solvents were concentrated. The crude material was redissolved in methanol (18 ml) followed by addition of sodium borohydride (49 mg, 1.29 mmol). After stirring for 40 minutes at room temperature, the mixture was partitioned between ethyl acetate (100 ml) and a saturated aqueous solution of sodium hydrogen carbonate (100 ml). After separation of the two phases the aqueous phase was re-extracted with ethyl acetate (100 ml). The combined organic layers were dried (Na2SO4), filtered and concentrated. Flash column chromatography on silica, eluting with 10% methanol in dichloromethane gave 4-(4-chloro-phenyl)-4-methylaminomethyl-piperidine-1-carboxylic acid tert-butyl ester (142 mg, 0.42 mmol, 68%). GC-MS m/z 239 [(M-Boc)+], Rt 5.18 min. 1H NMR (250 MHz, CDCl3): 1.43 (9H, s), 1.80-1.88 (2, m), 2.15-2.24 (2, m), 2.31 (3H, s), 2.81 (2H, s), 2.98-3.09 (2H, m), 3.72-3.78 (2H, m), 7.32 (2H, d, 9 Hz), 7.38 (2H, d, 9 Hz).

後処理

  1. concentrationThe solvents were concentrated
  2. dissolutionThe crude material was redissolved in methanol (18 ml)
  3. stirringAfter stirring for 40 minutes at room temperature
  4. customthe mixture was partitioned between ethyl acetate (100 ml)
  5. customAfter separation of the two phases the aqueous phase
  6. extractionwas re-extracted with ethyl acetate (100 ml)
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washFlash column chromatography on silica, eluting with 10% methanol in dichloromethane

出典と根拠

ORDレコード
ord-259eefef7b984a7c8f7e0e0a6df68642
出典データセット
uspto-grants-2015_04
特許番号
US09006430B2

反応ノート

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