Triethylamine → tert-Butyl 4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

HRID 471087

反応式

HRID 471087 の反応式
Cl.[O:2]1[C:7]2([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[CH2:6][NH:5][CH2:4][CH2:3]1.[CH:20]([C:23]1[S:24][CH:25]=[C:26]([C:28](O)=[O:29])[N:27]=1)([CH3:22])[CH3:21].C(N(CC)CC)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CC1OCCC1.C1COCC1.O>[CH:20]([C:23]1[S:24][CH:25]=[C:26]([C:28]([N:5]2[CH2:6][C:7]3([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]3)[O:2][CH2:3][CH2:4]2)=[O:29])[N:27]=1)([CH3:22])[CH3:21]

参加物

8

反応物 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 225730652-(Propan-2-yl)-1,3-thiazole-4-carboxylic acidHCID 66964240Tert-butyl 1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride

生成物 1

HCID 57989200tert-Butyl 4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate収率 89%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 73012-Methyltetrahydrofuran溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
12.5 °C

実験手順

A mixture of tert-butyl 1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (limiting reagent) and 2-isopropylthiazole-4-carboxylic acid (1.1 molar equivalents) was suspended in 2-MeTHF (10 volumes) and cooled to 10-15° C. Triethylamine (7.2 molar equivalents) was added in portions at 10-15° C. The thick suspension was cooled to 5-10° C. and T3P (1.3 molar equivalents of a 1.57M solution in THF) was added dropwise at 5-10° C. over 0.5 hr. The reaction mixture was allowed to warm to ambient temperature (35 min) and stirred for 2.5 hr. The mixture was diluted with water (10 volumes, 5° C. exotherm) and the mixture vigorously stirred; the aqueous (pH 10) was separated and extracted with 2-MeTHF (2×2 volumes). The combined organics were washed with saturated aq sodium bicarbonate soln (2 volumes) and water (2×2 volumes). The organic phase was evaporated and azeotroped with MeCN (2×2 volumes) to give a brown gum, which was dried at 35° C. in vacuo for 24 hr. Yield: 89% of theoretical.

後処理

  1. temperatureThe thick suspension was cooled to 5-10° C.
  2. temperatureto warm to ambient temperature (35 min)
  3. stirringthe mixture vigorously stirred
  4. customthe aqueous (pH 10) was separated
  5. extractionextracted with 2-MeTHF (2×2 volumes)
  6. washThe combined organics were washed with saturated aq sodium bicarbonate soln (2 volumes) and water (2×2 volumes)
  7. customThe organic phase was evaporated
  8. customazeotroped with MeCN (2×2 volumes)
  9. customto give a brown gum, which
  10. customwas dried at 35° C. in vacuo for 24 hr

出典と根拠

ORDレコード
ord-7b13b7de648e44f9ad6bf02edfa155b5
出典データセット
uspto-grants-2014_01
特許番号
US08629271B2

関連ノート

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