Hydrochloric Acid → 6-[(1S)-1,3-Dihydroxy-1-[1-(triphenylmethyl)-1H-imidazol-4-yl]propyl]-N-methyl-2-naphthalenecarboxamide

HRID 1444949ノート

反応式

HRID 1444949 の反応式
[BH4-].[Na+].[Cl-].[Ca+2].[Cl-].[OH:6][C@@:7]([C:40]1[CH:49]=[CH:48][C:47]2[C:42](=[CH:43][CH:44]=[C:45]([C:50]([NH:52][CH3:53])=[O:51])[CH:46]=2)[CH:41]=1)([C:16]1[N:17]=[CH:18][N:19]([C:21]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:20]=1)[CH2:8][C:9](OC(C)(C)C)=[O:10].Cl>C(OCC)(=O)C.O.C1COCC1.C(O)C>[OH:6][C@@:7]([C:40]1[CH:41]=[C:42]2[C:47](=[CH:48][CH:49]=1)[CH:46]=[C:45]([C:50]([NH:52][CH3:53])=[O:51])[CH:44]=[CH:43]2)([C:16]1[N:17]=[CH:18][N:19]([C:21]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:20]=1)[CH2:8][CH2:9][OH:10]

参加物

9

反応物 4

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 5284359Calcium ChlorideHCID 57465810tert-butyl(3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate

生成物 1

HCID 574658086-[(1S)-1,3-Dihydroxy-1-[1-(triphenylmethyl)-1H-imidazol-4-yl]propyl]-N-methyl-2-naphthalenecarboxamide収率 61%

試薬・触媒・溶媒 4

HCID 702Ethanol溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

6.5 mL of ethanol and 6.5 mL of THF were added to 0.47 g (12.5 mmol, 8 eq) of sodium borohydride. 0.7 g (6.27 mmol, 4 eq) of calcium chloride was added at 4˜5° C., and the mixture was stirred at 4˜5° C. for 35 minutes. 1 g (1.57 mmol) of tert-butyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate was added at 5° C. The mixture was stirred at 23˜29° C. for 6 hours. 35 mL of water was added dropwise. 12.5 mL of 1N hydrochloric acid was added dropwise, diluted with 20 mL of ethyl acetate, and the layers were separated. The aqueous layer was re-extracted with 20 mL of ethyl acetate. The organic layers were combined, and washed successively with 10 mL of water and 10 mL of an aqueous saturated sodium chloride solution. After concentrated under reduced pressure, the concentration residue was dissolved in 1 mL of ethanol, and allowed to stand overnight. Crystals were filtered, and washed with 0.2 mL of ethanol. The filtrate was concentrated under reduced pressure, 0.5 mL of ethyl acetate and 1 mL of IPE were added to the concentration residue, crystals were loosened, filtered, and washed with 0.75 mL of ethyl acetate/IPE=1/10.75 ml. Vacuum drying (40° C.) to a constant weight afforded 0.5 g of 6-[(1S)-1,3-dihydroxy-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (yield 61%).

後処理

  1. stirringThe mixture was stirred at 23˜29° C. for 6 hours
  2. customthe layers were separated
  3. extractionThe aqueous layer was re-extracted with 20 mL of ethyl acetate
  4. washwashed successively with 10 mL of water and 10 mL of an aqueous saturated sodium chloride solution
  5. concentrationAfter concentrated under reduced pressure
  6. dissolutionthe concentration residue was dissolved in 1 mL of ethanol
  7. waitto stand overnight
  8. filtrationCrystals were filtered
  9. washwashed with 0.2 mL of ethanol
  10. concentrationThe filtrate was concentrated under reduced pressure, 0.5 mL of ethyl acetate and 1 mL of IPE
  11. additionwere added to the concentration residue, crystals
  12. filtrationfiltered
  13. washwashed with 0.75 mL of ethyl acetate/IPE=1/10.75 ml
  14. customVacuum drying (40° C.) to a constant weight

出典と根拠

ORDレコード
ord-35bba36c6f3a45dfb1476e4b59d24c59
出典データセット
uspto-grants-2010_02
特許番号
US07662974B2

反応ノート

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