Hydrochloric Acid → HCID 178447302, compound

HRID 550047Notes

Reaction equation

HRID 550047 reaction equation
[CH3:1][CH:2]([CH3:26])[C@H:3]([NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[C:21]2[NH:25][N:24]=[N:23][N:22]=2)=[CH:11][CH:10]=1)[C:4]([OH:6])=[O:5].[C:27](Cl)(=[O:32])[CH2:28][CH2:29][CH2:30][CH3:31].N1C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].Cl>COCCOC.C(OC(=O)C)C>[CH3:1][CH:2]([CH3:26])[C@H:3]([N:7]([C:27](=[O:32])[CH2:28][CH2:29][CH2:30][CH3:31])[CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[C:21]2[NH:22][N:23]=[N:24][N:25]=2)=[CH:13][CH:14]=1)[C:4]([OH:6])=[O:5]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 10340Sodium CarbonateHCID 61186Valeryl chlorideHCID 178448321HCID 178448321, compound

Product 1

HCID 178447302HCID 178447302, compound

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-5 °C

Procedure

A suspension of (S)-3-methyl-2-((2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl)-amino)-butyric acid (17.6 g; 50.0 mmol) in 1,2-dimethoxyethan (116 g) is cooled to −5° C., and valeroyl-chloride (9.9 ml; 80 mmol) is added, followed by slow addition of pyridine (6.0 ml; 75 mmol) diluted with 1,2-dimethoxyethane (60 ml). [1] After completion of the reaction, the reaction mixture is quenched with methanol (18 ml). Finally water (50 ml) is added at room temperature, and after stirring for 1 h, the mixture is adjusted to pH 7.5 by addition of aqueous sodium carbonate solution 10% (˜116 ml, 120 mmol) at 0° C. The organic solvents are stripped off at 50° C. in vacuo. Ethylacetate (125 ml) is added to the remaining aqueous concentrate, and the two-phase system is adjusted to pH 2 at 0-5° C. by addition of 2.0 M HCl (˜98 ml). The organic phase is separated and concentrated at 45° C. in vacuo (water is azeotropically removed). The crystallization of the product is initiated at 45° C. and—after addition of cyclohexan (102 ml)—completed by cooling to −5° C. The solid is collected by filtration, and after drying at 50° C., (S)-3-methyl-2-{pentanoyl-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-amino}-butyric acid is received as a white powder.

Workup

  1. customthe reaction mixture is quenched with methanol (18 ml)
  2. additionFinally water (50 ml) is added at room temperature
  3. customare stripped off at 50° C. in vacuo
  4. customThe organic phase is separated
  5. concentrationconcentrated at 45° C. in vacuo (water
  6. customis azeotropically removed)
  7. customThe crystallization of the product
  8. customis initiated at 45° C.
  9. addition—after addition of cyclohexan (102 ml)
  10. temperatureby cooling to −5° C
  11. filtrationThe solid is collected by filtration
  12. customafter drying at 50° C.

Sources & evidence

ORD record
ord-da616dd016b24524ae8c85c2cd999c91
Source dataset
uspto-grants-2011_05
Patent number
US07943647B2

Reaction notes

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