Diisopropylethylamine → Ethyl (2E,4S)-4-[{N-[(2R)-2-(1-adamantyl)-2-(methylamino)ethanoyl]-3-methyl-L-valyl}(methyl)amino]-2,5-dimethyl-2-hexenoate

HRID 133810Notes

Reaction equation

HRID 133810 reaction equation
[C:1]12([CH:11]([NH:15][CH3:16])[C:12]([OH:14])=O)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[CH3:50]/[C:51](=[CH:57]\[C@@H:58]([N:62]([CH3:71])[C:63](=[O:70])[C@H:64]([C:66]([CH3:69])([CH3:68])[CH3:67])[NH2:65])[CH:59]([CH3:61])[CH3:60])/[C:52]([O:54][CH2:55][CH3:56])=[O:53].C(N(C(C)C)CC)(C)C>ClCCl>[C:1]12([C@@H:11]([NH:15][CH3:16])[C:12]([NH:65][C@H:64]([C:63]([N:62]([CH3:71])[C@@H:58]([CH:59]([CH3:61])[CH3:60])/[CH:57]=[C:51](\[CH3:50])/[C:52]([O:54][CH2:55][CH3:56])=[O:53])=[O:70])[C:66]([CH3:69])([CH3:68])[CH3:67])=[O:14])[CH2:10][CH:5]3[CH2:4][CH:3]([CH2:9][CH:7]([CH2:6]3)[CH2:8]1)[CH2:2]2

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 11120545ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoateHCID 11229817Adamantan-1-yl-methylamino-acetic acid

Product 1

HCID 86596600Ethyl (2E,4S)-4-[{N-[(2R)-2-(1-adamantyl)-2-(methylamino)ethanoyl]-3-methyl-L-valyl}(methyl)amino]-2,5-dimethyl-2-hexenoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To adamantan-1-yl-methylamino-acetic acid (0.447 g, 2.0 mmol, from Reference Example 6) in dichloromethane (17 mL) is added PyBOP (1.04 g, 2.0 mmol). After 15 min ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoate (0.625 g, 2.0 mmol, WO 99/32509) in dichlormethane (5 mL) is added, followed by diisopropylethylamine (0.75 mL, 4.3 mmol). This is stirred at room temperature overnight. The reaction mixture is evaporated in vacuo and the residue treated with ethyl acetate and water. The ethyl acetate layer is dried over sodium sulfate and purified by hplc. The two diastereomers are partially separated. The first isomer is assigned the SSS configuration and contained 33.4% of the RSS isomer. MS: m/z 518.3 (M+1). The second isomer is assigned the RSS configuration and contained 8.9% of the SSS isomer. MS: m/z 518.3 (M+1).

Workup

  1. customThe reaction mixture is evaporated in vacuo
  2. additionthe residue treated with ethyl acetate and water
  3. dry with materialThe ethyl acetate layer is dried over sodium sulfate
  4. custompurified by hplc
  5. customThe two diastereomers are partially separated

Sources & evidence

ORD record
ord-a48711c029d742829bfac315dffebdea
Source dataset
uspto-grants-2008_06
Patent number
US07390910B2

Reaction notes

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