Diisopropylethylamine → tert-butyl (2R)-3-(benzyloxy)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-ylcarbamate

HRID 1036683ノート

反応式

HRID 1036683 の反応式
[CH2:1]([O:8][CH2:9][C@@H:10]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:11]([OH:13])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C.[CH3:49][N:50]1[CH2:54][C@H:53]([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[C@:52]2([CH2:65][CH2:64][CH2:63][NH:62][CH2:61]2)[C:51]1=[O:66].CN1C[C@@H](C2C=CC=CC=2)[C@@]2(CCCNC2)C1=O>CC#N.Cl>[CH2:1]([O:8][CH2:9][C@@H:10]([NH:14][C:15](=[O:16])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[C:11]([N:62]1[CH2:63][CH2:64][CH2:65][C:52]2([C:51](=[O:66])[N:50]([CH3:49])[CH2:54][CH:53]2[C:55]2[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=2)[CH2:61]1)=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

8

反応物 5

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 2733693(R)-3-(benzyloxy)-2-((tert-butoxycarbonyl)amino)propanoic acidHCID 71060185(4S,5R)-2-Methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one2 回HCID 71060283(4R,5S)-2-Methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one

生成物 1

HCID 86674095tert-butyl (2R)-3-(benzyloxy)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-ylcarbamate

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid溶媒HCID 6342Acetonitrile溶媒

実験手順

A mixture comprising (R)-3-(benzyloxy)-2-(tert-butoxycarbonylamino)propanoic acid (Sigma-Aldrich) (1.052 g, 3.56 mmol) and ®T3P (50% in EtOAc) (4.16 ml, 7.12 mmol) in MeCN (20 mL) was treated dropwise with DIPEA (2.488 ml, 14.25 mmol). The resulting solution was stirred at room temperature for 30 minutes, then a racemic mixture of (4R,5S)-2-Methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one and (4S,5R)-2-Methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one (Intermediate 1A) (1 g, 3.56 mmol) was added portionwise. The reaction mixture was stirred for 20 hours at room temperature. The reaction mixture was diluted with 0.1M HCl (20 mL) and extracted with DCM (20 mL). The aqueous phase was further extracted with DCM (3×20 mL). The combined organic portions were washed with a saturated solution of sodium bicarbonate (20 mL), water (20 mL), dried (MgSO4), and concentrated in vacuo to afford the title compound. No purification was performed on the title compound.

後処理

  1. additionwas added portionwise
  2. stirringThe reaction mixture was stirred for 20 hours at room temperature
  3. extractionextracted with DCM (20 mL)
  4. extractionThe aqueous phase was further extracted with DCM (3×20 mL)
  5. washThe combined organic portions were washed with a saturated solution of sodium bicarbonate (20 mL), water (20 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-d8eb3aa6e5384a1a892868ecf4447f40
出典データセット
uspto-grants-2013_10
特許番号
US08546416B2

反応ノート

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