Hydrochloric Acid → HCID 131714426, compound

HRID 652357Notes

Reaction equation

HRID 652357 reaction equation
[NH2:1][C@@H:2]([CH2:33][CH:34]([CH3:36])[CH3:35])[CH:3]([OH:32])[CH2:4][N:5](C(OCC1C=CC=CC=1)=O)[C@H:6]([C:11]([NH:13][C@H:14]([C:18]([O:20][CH3:21])=[O:19])[CH:15]([CH3:17])[CH3:16])=[O:12])[CH2:7][CH:8]([CH3:10])[CH3:9].C(OC(N[C@@H](CC(C)C)C(O)CN(C(OCC1C=CC=CC=1)=O)[C@H](C(OCC[Si](C)(C)C)=O)CC(C)C)=O)(C)(C)C.[ClH:78].[H][H].O>CO.[Pd].C(Cl)(Cl)Cl>[ClH:78].[ClH:78].[NH2:1][C@@H:2]([CH2:33][CH:34]([CH3:36])[CH3:35])[CH:3]([OH:32])[CH2:4][NH:5][C@H:6]([C:11]([NH:13][C@H:14]([C:18]([O:20][CH3:21])=[O:19])[CH:15]([CH3:16])[CH3:17])=[O:12])[CH2:7][CH:8]([CH3:10])[CH3:9]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 57126841HCID 57126841, compoundHCID 131714424HCID 131714424, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 131714426HCID 131714426, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×HCID 6212ChloroformSolvent

Procedure

A solution of 109 mg of (3S)-N-[N-(3-amino-2-hydroxy-5-methylhexyl)-N-[(phenylmethoxy)carbonyl]-L-leucyl]-L-valine, methyl ester (Isomer B, prepared from N-[(3S)-3-[[(t-butyloxy)carbonyl]amino]-2-hydroxy-5-methylhexyl]-N-[(phenylmethoxy)carbonyl]-L-leucine, 2-(trimethylsilyl)ethyl ester, Isomer B using a procedure analogous to that described in Example 8 for preparing the corresponding Isomer A) in 3 ml of methanol was treated with 0.63 ml of 1N hydrochloric acid and 75 mg of 10% palladium on charcoal and subjected to a steady stream of hydrogen at 1 atmosphere pressure. After 3 hours, a silica gel TLC run in 9:1, chloroform:methanol, checked with UV and PMA, indicated complete disappearance of the starting compound. The reaction was worked up by filtering through a Celite pad, concentrating the filtrate in vacuo, and recrystallizing the residue from methanol/ether at room temperature, then storing in the freezer overnight to afford 73 mg of partially purified product, melting at 232°-234° C. Chromatography was performed on a 35 ml column of HP-20 resin, eluting with a gradient from 175 ml of 96:3:1 to 2:2:96, water: 1N hydrochloric acid:methanol. The fractions were checked by silica gel TLC run in 5:1:1:1, butanol:pyridine:acetic acid:water and sprayed with ninhydrin. Pooling of product containing fractions followed by lyophilization yielded 17 mg of the title compound as a hydrate with 1.0 mole of water, melting point 125°-140° C.

Workup

  1. filtrationby filtering through a Celite pad
  2. concentrationconcentrating the filtrate in vacuo
  3. customrecrystallizing the residue from methanol/ether at room temperature
  4. customstoring in the freezer overnight
  5. customto afford 73 mg of partially purified product, melting at 232°-234° C
  6. washeluting with a gradient from 175 ml of 96:3:1 to 2:2:96, water
  7. additionPooling of product containing fractions

Sources & evidence

ORD record
ord-8d012bf132324436a0b1673be5da78bb
Source dataset
uspto-grants-1987_06
Patent number
US04670541

Reaction notes

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