(S)-4-(3-tert-butoxycarbonylmethyl-ureido)-5-(3'-chloro-biphenyl-4-yl)-2-methyl-pentanoic acid ethyl ester → (2R,4S)-4-(3-Carboxymethyl-ureido)-5-(3'-chloro-biphenyl-4-yl)-2-methyl-pentanoic acid ethyl ester

HRID 2384048Notes

Reaction equation

HRID 2384048 reaction equation
[CH2:1]([O:3][C:4](=[O:35])[C@@H:5]([CH3:34])[CH2:6][CH:7]([NH:22][C:23]([NH:25][CH2:26][C:27]([O:29]C(C)(C)C)=[O:28])=[O:24])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)=[CH:11][CH:10]=1)[CH3:2]>C(Cl)Cl.C(O)(C(F)(F)F)=O>[CH2:1]([O:3][C:4](=[O:35])[C@H:5]([CH3:34])[CH2:6][C@H:7]([NH:22][C:23]([NH:25][CH2:26][C:27]([OH:29])=[O:28])=[O:24])[CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)=[CH:13][CH:14]=1)[CH3:2]

Participants

3

Reactant 1

HCID 67506149(S)-4-(3-tert-butoxycarbonylmethyl-ureido)-5-(3'-chloro-biphenyl-4-yl)-2-methyl-pentanoic acid ethyl ester

Product 1

HCID 59608183(2R,4S)-4-(3-Carboxymethyl-ureido)-5-(3'-chloro-biphenyl-4-yl)-2-methyl-pentanoic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

Next, a solution of (S)-4-(3-tert-butoxycarbonylmethyl-ureido)-5-(3′-chloro-biphenyl-4-yl)-2-methyl-pentanoic acid ethyl ester (261 mg, 59.1 mmol) in 8 mL of methylene chloride/TFA (1:1) is stirred at room temperature for 1 hour. The solvent is removed under reduced pressure and the residue is purified by preparative HPLC using a gradient of 10% MeCN/water to 100% MeCN (0.1% TFA) and the product is further purified by chiral HPLC on a Chirapak OD-H column using heptane/ethanol (90:10) (0.1% TFA) to elute the title compound; HPLC Retention time 1.48 minutes (condition C): MS 447.3 (M+1); 1H NMR (400 MHz, DMSO-d6): δ ppm 1.03-1.05 (d, J=7.07 Hz, 3H), 1.08-1.12 (t, J=7.33 Hz, 3H), 1.27-1.34 (m, 1H), 1.70-1.76 (m, 1H), 2.62-2.67 (m, 1H), 2.71-2.76 (m, 2H), 3.66-3.68 (d, J=5.81 Hz, 2H), 3.71-3.78 (m, 1H), 3.95-4.00 (q, J=7.07 Hz, 14.40 Hz, 2H), 5.94-5.97 (t, J=5.56 Hz, 1H), 6.07-6.09 (d, J=8.34 Hz, 1H), 7.25-7.28 (m, 2H), 7.38-7.41 (m, 1H), 7.45-7.49 (t, J=7.83 Hz, 1H), 7.60-7.63 (m, 3H), 7.69-7.70 (t, J=1.77 Hz, 1H), 12.42 (s, 1H).

Workup

  1. customThe solvent is removed under reduced pressure
  2. customthe residue is purified by preparative HPLC
  3. customthe product is further purified by chiral HPLC on a Chirapak OD-H column
  4. washto elute the title compound

Sources & evidence

ORD record
ord-151c38fb9e83446896dd5a7e8f38581a
Source dataset
uspto-grants-2012_09
Patent number
US08263629B2

Reaction notes

Loading…