Methanol → (3R)-2-(tert-butoxycarbonylamino)-3,5-dimethylnon-8-enoic acid

HRID 1852176Notes

Reaction equation

HRID 1852176 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C@H:15]([CH3:23])[CH2:16][CH:17]([CH3:22])[CH2:18][CH2:19][CH:20]=[CH2:21])[C:10]([O:12]CC)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CO.[Li+].[OH-]>C1COCC1.O>[C:1]([O:5][C:6]([NH:8][CH:9]([C@H:15]([CH3:23])[CH2:16][CH:17]([CH3:22])[CH2:18][CH2:19][CH:20]=[CH2:21])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 86683235(3R)-ethyl 2-(tert-butoxycarbonylamino)-3,5-dimethylnon-8-enoate

Product 1

HCID 86683236(3R)-2-(tert-butoxycarbonylamino)-3,5-dimethylnon-8-enoic acidYield 68%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a solution of (3R)-ethyl 2-(tert-butoxycarbonylamino)-3,5-dimethylnon-8-enoate (20 g, 0.061 moles) in THF/water (200 mL, 1:1) was added methanol (60 mL) followed by LiOH (7.7 g, 0.183 moles) at room temperature. The reaction mass was stirred at room temperature overnight. The solution was concentrated under reduced pressure and the residue was diluted with water (200 mL). The aqueous solution was acidified with aqueous 1.5 N HCl solution to pH ˜3 and extracted with ethyl acetate (100 mL×3). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduce pressure to get crude compound. The crude compound was purified by column chromotography (Silica gel, 3% methanol in DCM) to get 12.4 g (68%) of (3R)-2-(tert-butoxycarbonylamino)-3,5-dimethylnon-8-enoic acid as gummy liquid. 1H NMR (400 MHz, DMSO-d6): δ ppm 12.4 (sb, 1H), 6.92-6.85 (m, 1H), 5.81-5.75 (m, 1H), 5.04-4.93 (m, 2H), 4.12-3.91 (m, 1H), 2.18-1.98 (m, 4H), 1.5 (s, 9H), 1.35-1.02 (m, 3H), 0.98-0.85 (m, 6H).

Workup

  1. concentrationThe solution was concentrated under reduced pressure
  2. additionthe residue was diluted with water (200 mL)
  3. extractionextracted with ethyl acetate (100 mL×3)
  4. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customto get crude compound
  7. customThe crude compound was purified by column chromotography (Silica gel, 3% methanol in DCM)

Sources & evidence

ORD record
ord-b8e692ad82a1453da96ed3add6c4450f
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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