Thionyl Chloride → HCID 66584612, compound

HRID 1525638Notes

Reaction equation

HRID 1525638 reaction equation
[C:1]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([NH:15]C(OC(C)(C)C)=O)/[CH:9]=[C:10](/[CH3:14])\[C:11]([OH:13])=[O:12])=[CH:3][CH:2]=1.S(Cl)([Cl:31])=O>C(O)C>[ClH:31].[NH2:15][C@H:8]([CH2:7][C:4]1[CH:3]=[CH:2][C:1]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[CH:6][CH:5]=1)/[CH:9]=[C:10](/[CH3:14])\[C:11]([OH:13])=[O:12]

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 56847899Sacubitril Impurity 72

Product 1

HCID 66584612HCID 66584612, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
65 °C

Procedure

5 g (Z)—(R)-5-Biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpent-2-enoic acid (5a, R1=Boc, R2=H, R3=CO2H) is added to ethanol (50 ml) at room temperature. The mixture was stirred for 15 min and a further quantity of ethanol (10 ml) added. The mixture is then heated to 65° C. Thionyl chloride (1.44 ml) is added and the mixture stirred for 30 min. The volatiles are removed under reduced pressure. Heptane (50 ml) is added to the residue and the volatiles removed under reduced pressure. Ethyl acetate (30 ml) is added to the residue. The solid is collected by filtration. A portion of the solid (1 g) is suspended in ethyl acetate and stirred for 1 h at room temperature. The solid is collected by filtration and dried in vacuo to afford (Z)—(R)-4-amino-5-biphenyl-4-yl-2-methyl-pent-2-enoic acid hydrochloride (5a, R1=H, R2=H, R3=CO2H). 1H-NMR (DMSO): 1.79 (3H), 2.88 (1H), 3.10 (1H), 4.79 (1H), 5.91 (1H), 7.24-7.60 (9H), 8.32 (3H), 12.90 (1H).

Workup

  1. stirringthe mixture stirred for 30 min
  2. customThe volatiles are removed under reduced pressure
  3. additionHeptane (50 ml) is added to the residue
  4. customthe volatiles removed under reduced pressure
  5. additionEthyl acetate (30 ml) is added to the residue
  6. filtrationThe solid is collected by filtration
  7. stirringstirred for 1 h at room temperature
  8. filtrationThe solid is collected by filtration
  9. customdried in vacuo

Sources & evidence

ORD record
ord-d1d3c7659a674f919d0a47b6a0e789e2
Source dataset
uspto-grants-2015_07
Patent number
US09085529B2

Reaction notes

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