Sodium Hydroxide → methyl 4-[[(1S,4S)-5-[[4-[4-(2-oxazolyl)phenoxy]phenyl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoate

HRID 16510ノート

反応式

HRID 16510 の反応式
[O:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[CH:20]=[CH:19][C:9]([O:10][C:11]2[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=2)=[CH:8][CH:7]=1.[C@H:21]12[CH2:27][C@H:24]([NH:25][CH2:26]1)[CH2:23][N:22]2[CH2:28][C:29]1[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClC(Cl)C>[O:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[CH:20]=[CH:19][C:9]([O:10][C:11]2[CH:18]=[CH:17][C:14]([CH2:15][N:25]3[CH2:26][C@@H:21]4[CH2:27][C@H:24]3[CH2:23][N:22]4[CH2:28][C:29]3[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=3)=[CH:13][CH:12]=2)=[CH:8][CH:7]=1

参加物

6

反応物 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 68488731methyl 4-[[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoateHCID 866134384-(4-(2-Oxazolyl)phenoxy)benzaldehyde

生成物 1

HCID 68487965methyl 4-[[(1S,4S)-5-[[4-[4-(2-oxazolyl)phenoxy]phenyl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoate収率 100%

試薬・触媒・溶媒 1

HCID 63651,1-Dichloroethane溶媒

実験手順

4-[4-(2-oxazolyl)phenoxy]benzaldehyde (10.2 g, 38.5 mmol) and methyl 4-[[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoate (9.9 g, 40.4 mmol, 1.05 equiv.) were dissolved in dichloroethane (200 mL). After 75 minutes, sodium triacetoxyborohydride (9.8 g, 46.1 mmol, 1.2 equiv.) was added. The reaction mixture was stirred overnight at ambient temperature. Then, 1N NaOH was added. The reaction mixture was separated and the aqueous layer was extracted with CH2Cl2. The combined organic layers were washed with 0.5 M H2SO4, and MeOH was added to the mixture until the precipitated gummy solid dissolved. The layers were separated and the aqueous layer was cooled to −5 C. and saturated K2CO3 was added slowly enough to keep the temperature below 0 C. to prevent ester hydrolysis. Once the pH was 11, the solution was extracted with EtOAc (2×), and the combined EtOAc fractions were dried and concentrated to give 19.0 g (100%) of methyl 4-[[(1S,4S)-5-[[4-[4-(2-oxazolyl)phenoxy]phenyl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoate as the free base, which was 98% pure by HPLC; 1H NMR (300 MHz, CDCl3) δ 8.02 (d, 2H), 8.02 (d, 2H), 7.69 (d, 1H), 7.47 (d, 2H), 7.40 (d, 2H), 7.22 (d, 1H), 7.08 (d, 2H), 7.05 (d, 2H), 3.92 (s, 3H), 3.84 (d, 1H), 3.78 (d, 1H), 3.77 (d, 1H), 3.71 (d, 1H), 3.35 (s, 1H), 3.31 (s, 1H), 2.89 (d, 1H), 2.88 (d, 1H), 2.71 (dd, 1H), 2.70 (dd, 1H), 1.79 (s, 2H) ppm.

後処理

  1. customThe reaction mixture was separated
  2. extractionthe aqueous layer was extracted with CH2Cl2
  3. washThe combined organic layers were washed with 0.5 M H2SO4, and MeOH
  4. additionwas added to the mixture until the precipitated gummy solid
  5. dissolutiondissolved
  6. customThe layers were separated
  7. temperaturethe aqueous layer was cooled to −5 C
  8. additionand saturated K2CO3 was added slowly enough
  9. customester hydrolysis
  10. extractionOnce the pH was 11, the solution was extracted with EtOAc (2×)
  11. dry with materialthe combined EtOAc fractions were dried
  12. concentrationconcentrated

出典と根拠

ORDレコード
ord-c469e95f96b64d84919d8c5e749dbe3f
出典データセット
uspto-grants-2010_06
特許番号
US07737145B2

反応ノート

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