Sodium Hydroxide → HCID 59608157, compound

HRID 1469610Notes

Reaction equation

HRID 1469610 reaction equation
C([O:3][C:4](=[O:33])[C@H:5]([CH3:32])[CH2:6][C@H:7]([NH:21][C:22]([C:24]1[S:25][C:26]([C:29](=[O:31])[NH2:30])=[CH:27][CH:28]=1)=[O:23])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)C.[OH-].[Na+]>C(O)C>[C:12]1([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:11]=[CH:10][C:9]([CH2:8][C@@H:7]([NH:21][C:22]([C:24]2[S:25][C:26]([C:29](=[O:31])[NH2:30])=[CH:27][CH:28]=2)=[O:23])[CH2:6][C@@H:5]([CH3:32])[C:4]([OH:33])=[O:3])=[CH:14][CH:13]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 67505791HCID 67505791, compound

Product 1

HCID 59608157HCID 59608157, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

Next, to a solution of (2R,4S)-5-biphenyl-4-yl-4-[(5-carbamoyl-thiophene-2-carbonyl)-amino]-2-methyl-pentanoic acid ethyl ester (115 mg, 0.248 mmol) in ethanol (8 mL) is added aqueous 1M NaOH (0.866 mL, 0.866 mmol) and the mixture is stirred at 50° C. for 3.5 hours. The ethanol is removed under reduced pressure and water is added to the residue. The resulting solution is acidified with aqueous 1M HCl and the resulting precipitate is filtered and washed with water. The solid is purified by preparative HPLC using 50% MeCN/water to elute the product. The appropriate fractions are lyophilized to give (2R,4S)-5-biphenyl-4-yl-4-[(5-carbamoyl-thiophene-2-carbonyl)-amino]-2-methyl-pentanoic acid. MS 437.2 (M+1); 1H-NMR (400 MHz, DMSO-d6); δ ppm 1.09 (d, J=7.20Hz, 3H), 1.57 (m, 1H), 1.88 (m, 1H), 2.46 (m, 1H), 2.84 (m, 2H), 4.18 (m, 1H), 7.28 (d, J=8.21Hz, 1H), 7.33 (t, 1H), 7.44 (t, 1H), 7.57 (d, J=8.21Hz, 2H), 7.64 (d, J=7.33, 2H), 7.69 (m, 2H), 8.06 (s, 1H), 8.38 (d, J=8.59Hz, 1H), 12.07 (s, broad, 1H).

Workup

  1. customThe ethanol is removed under reduced pressure and water
  2. additionis added to the residue
  3. filtrationthe resulting precipitate is filtered
  4. washwashed with water
  5. customThe solid is purified by preparative HPLC
  6. washto elute the product

Sources & evidence

ORD record
ord-598dfc6ad90a4e87ade56002d013e3a0
Source dataset
uspto-grants-2015_04
Patent number
US09006249B2

Reaction notes

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