Lithium hydroxide, monohydrate → tert-butyl 5-chloro-1-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-carboxylate

HRID 529066ノート

反応式

HRID 529066 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]3)[CH2:9][N:8]([C:23]3[C:24]4[C@H:31]([CH3:32])[CH2:30][C@@H:29]([O:33]C(=O)C5C=CC([N+]([O-])=O)=CC=5)[C:25]=4[N:26]=[CH:27][N:28]=3)[C:5]2=[CH:6][CH:7]=1.O[Li].O>C1COCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][CH2:15]3)[CH2:9][N:8]([C:23]3[C:24]4[C@H:31]([CH3:32])[CH2:30][C@@H:29]([OH:33])[C:25]=4[N:26]=[CH:27][N:28]=3)[C:5]2=[CH:6][CH:7]=1

参加物

4

反応物 2

HCID 168937Lithium hydroxide, monohydrateHCID 68762968HCID 68762968、化合物

生成物 1

HCID 68759438tert-butyl 5-chloro-1-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-carboxylate収率 36%

試薬・触媒・溶媒 1

HCID 21881883Oxolane--water (1/1)溶媒

反応条件

温度
0 °C

実験手順

A solution of tert-butyl 5-chloro-1-((5R,7R)-5-methyl-7-(4-nitrobenzoyloxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.020 g, 0.032 mmol) in THF:H2O (2:1, 0.3 mL) was cooled to about 0° C. and treated with LiOH—H2O (0.0027 g, 0.065 mmol). The reaction was stirred at about 0° C. for about 5 minutes, followed by about room temperature for 1.5 hours. The reaction was concentrated and diluted with saturated NaHCO3 and extracted with EtOAc. The combined extracts were washed with brine, dried over MgSO4, filtered and concentrated. Crude residue was purified by preparative HPLC to yield tert-butyl 5-chloro-1-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.005 g, 36%). LCMS (APCI+) m/z 471, 473 [M+H]+; Rt=4.11 min.

後処理

  1. waitfollowed by about room temperature for 1.5 hours
  2. concentrationThe reaction was concentrated
  3. additiondiluted with saturated NaHCO3
  4. extractionextracted with EtOAc
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customCrude residue was purified by preparative HPLC

出典と根拠

ORDレコード
ord-455cfe1d29aa4f319f2a459d549987ef
出典データセット
uspto-grants-2016_05
特許番号
US09346805B2

反応ノート

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