1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → [4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]carbamic acid tert-butyl ester

HRID 554022

反応式

HRID 554022 の反応式
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C.[CH3:48][C:49]12[CH2:56][CH:53]([NH:54][CH2:55]1)[CH2:52][C:51]([CH3:58])([CH3:57])[CH2:50]2>C1COCC1>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]1[CH:10]=[CH:11][C:12]([C:13]([N:54]2[CH2:55][C:49]3([CH3:48])[CH2:56][CH:53]2[CH2:52][C:51]([CH3:58])([CH3:57])[CH2:50]3)=[O:15])=[CH:16][CH:17]=1)([CH3:2])([CH3:3])[CH3:4]

参加物

7

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1037871,3,3-Trimethyl-6-azabicyclo(3.2.1)octaneHCID 27559314-{[(Tert-butoxy)carbonyl]amino}benzoic acid

生成物 1

HCID 9907515[4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]carbamic acid tert-butyl ester収率 77.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a mixture of 4-tert-butoxycarbonylamino-benzoic acid (50 g, 0.21 mol) and HOBT (31.33 g, 0.231 mol) in dry THF (0.5 L) was added EDAC (44.44 g, 0.231 mol). The resulting mixture was stirred for 10 min followed by addition of a mixture of DIPEA (40.4 ml, 0.231 mol) and 1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane (39.4 ml, 0.231 mol). The reaction mixture was stirred for an additional 16 hrs. and evaporated to dryness. To the residue was added water (600 ml) and the resulting mixture was extracted with EtOAc (3×500 ml). The combined organic phases were dried (Na2SO4), filtered and evaporated in vacuo. The resulting residue was purified by column chromatography (silica gel) using a mixture of EtOAc-Heptane (1:2) as eluent. Pure fractions were collected and evaporated to dryness. To the solid residue was added diethyl ether (100 ml) and the precipitate was filtered off, washed with diethyl ether and dried in vacuo at 50° C. affording 60.5 g (77%) of [4-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]carbamic acid tert-butyl ester as a solid.

後処理

  1. stirringThe reaction mixture was stirred for an additional 16 hrs
  2. customand evaporated to dryness
  3. additionTo the residue was added water (600 ml)
  4. extractionthe resulting mixture was extracted with EtOAc (3×500 ml)
  5. dry with materialThe combined organic phases were dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe resulting residue was purified by column chromatography (silica gel)
  9. additiona mixture of EtOAc-Heptane (1:2) as eluent
  10. customPure fractions were collected
  11. customevaporated to dryness
  12. additionTo the solid residue was added diethyl ether (100 ml)
  13. filtrationthe precipitate was filtered off
  14. washwashed with diethyl ether
  15. customdried in vacuo at 50° C.

出典と根拠

ORDレコード
ord-8e60780f1f9849528669fe19b5e0ec32
出典データセット
uspto-grants-2011_11
特許番号
US08048908B2

関連ノート

読み込み中…