Water → HCID 15433299, compound

HRID 636851Notes

Reaction equation

HRID 636851 reaction equation
[C:1]([NH:5][C:6]([C@@H:8]1[CH2:17][C@H:16]2[C@H:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[CH2:10][N:9]1[CH2:18][C@@H:19]([OH:30])[C@@H:20]([NH2:29])[CH2:21][S:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])O.[Na+].O.[C:37]([O:40][C:41]1[C:42]([CH3:50])=[C:43]([CH:47]=[CH:48][CH:49]=1)[C:44](Cl)=[O:45])(=[O:39])[CH3:38]>C(OCC)(=O)C>[C:1]([NH:5][C:6]([C@@H:8]1[CH2:17][C@H:16]2[C@H:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[CH2:10][N:9]1[CH2:18][C@@H:19]([OH:30])[C@@H:20]([NH:29][C:44](=[O:45])[C:43]1[CH:47]=[CH:48][CH:49]=[C:41]([O:40][C:37](=[O:39])[CH3:38])[C:42]=1[CH3:50])[CH2:21][S:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962Water2×HCID 516892Sodium BicarbonateHCID 7010345(3-(Chlorocarbonyl)-2-methylphenyl)acetateHCID 9824208(3S,4aS,8aS)-2-[(2R,3R)-3-Amino-2-hydroxy-4-(phenylthio)butyl]-N-(1,1-dimethylethyl)decahydro-3-isoquinolinecarboxamide2×

Product 1

HCID 15433299HCID 15433299, compoundYield 101.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

(3S, 4aS, 8aS)-2-((2R, 3R)-3-Amino-2-hydroxy-4-phenylthiobutyl)-decahydroisoquinoline-3-carboxylic acid t-butylamide (compound [14], 9.39 g) and sodium hydrogencarbonate (4.55 g, 54.2 mmol) were added to a suspension of water (40 ml) and ethyl acetate (40 ml). A solution of 3-acetoxy-2-methylbenzoyl chloride (4.37 g, 20.6 mmol) in ethyl acetate (40 ml) was dropwise added to the suspension with stirring under ice-cooling. The mixture was further stirred for one hour under ice-cooling and water (20 ml) was added. The organic layer was separated and washed with a saturated aqueous solution (20 ml) of sodium hydrogencarbonate. After drying over magnesium sulfate, the solvent was distilled away under reduced pressure to give (3S, 4aS, 8aS)-2-[(2R, 3R)-3-(3-acetoxy-2-methylbenzoylamino)-2-hydroxy-4-phenylthiobutyl]decahydroisoquinoline-3-carboxylic acid t-butylamide (12.7 g, yield 96%) as colorless amorphous. 1H-NMR (CDCl3, 300 MHz) δ: 7.5-7.1 (m,8H), 7.1-7.0 (m,1H), 5.51 (brd.s,1H), 4.48 (m,1H), 4.07 (m,1H), 3.81 (dd,J=13.7,9.2Hz,1H), 3.41 (dd,J=13.7,4.7Hz,1H), 2.91 (dd,J=11.7,2.0Hz,1H), 2.56 (dd, J=12.9,9.1Hz,1H), 2.44 (m,1H), 2.32 (s,3H), 2.27 (s,3H), 2.3-2.1 (m,2H), 1.99 (m,1H), 1.9-1.1 (m,11H), 1.07 (s,9H)

Workup

  1. temperaturecooling
  2. stirringThe mixture was further stirred for one hour under ice-
  3. temperaturecooling
  4. customThe organic layer was separated
  5. washwashed with a saturated aqueous solution (20 ml) of sodium hydrogencarbonate
  6. dry with materialAfter drying over magnesium sulfate
  7. distillationthe solvent was distilled away under reduced pressure

Sources & evidence

ORD record
ord-304965f0dece4bdea3b5b403e994dab6
Source dataset
uspto-grants-2001_02
Patent number
US06194589B1

Reaction notes

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