Lithium Hydroxide → HCID 23299460, compound

HRID 1457714Notes

Reaction equation

HRID 1457714 reaction equation
[CH2:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH2:26][CH:25]([N:27]([S:34]([CH2:37][CH2:38][CH2:39][CH3:40])(=[O:36])=[O:35])[CH2:28][CH2:29][C:30]([O:32]C)=[O:31])[O:24][N:23]=3)=[CH:18][CH:17]=2)[CH2:10][CH2:9]1)=[O:7])[CH2:2][CH2:3][CH3:4].[Li+].[OH-]>C1COCC1>[CH2:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH2:26][CH:25]([N:27]([S:34]([CH2:37][CH2:38][CH2:39][CH3:40])(=[O:36])=[O:35])[CH2:28][CH2:29][C:30]([OH:32])=[O:31])[O:24][N:23]=3)=[CH:18][CH:17]=2)[CH2:10][CH2:9]1)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 23299510HCID 23299510, compound

Product 1

HCID 23299460HCID 23299460, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of the impure methyl 3-(3-[4-{(butyloxycarbonylpiperidin-4-yl)methoxy}phenyl]isoxazolin-5-yl{[butanesulfonyl]amino})propionate less polar diastereomer (309 mg) in THF (5 mL) was saponified using 0.5M LiOH (2 mL, 1 mmol) over 6 hours as per Example 1, Part F. The crude carboxylic acid was purified using flash chromatography (CHCl3 --5-15% MeOH/CHCl3 step gradient) followed by crystallization from EtOAc/hexanes, affording 169 mg of the desired material; mp: 155° C. (dec); 1H NMR (400 MHz, DMSO-d6, 80° C.) δ 7.56 (d, J=8.8 Hz, 2H), 6.98 (d, J=8.8 Hz, 2H), 4.80 (m, 1H), 3.96 (bd, J=13.2 Hz, 2H), 3.90 (d, J=6.3 Hz, 2H), 3.77 (bs, 3H), 3.52 (t, J=7.8 Hz, 1H), 3.38 (dd, J=14.4, 10.0 Hz, 1H), 2.98 (t, J=7.8 Hz, 2H), 2.76 (dt, J=12.2, 1.7 Hz, 2H), 1.95 (m, 2H), 1.75 (m, 4H), 1.41 (s, 9H), 1.38 (d, J=7.6 Hz, 1H), 1.25 (m, 4H), 0.88 (t, J=7.3 Hz, 3H).

Workup

  1. customover 6 hours
  2. customThe crude carboxylic acid was purified
  3. customfollowed by crystallization from EtOAc/hexanes

Sources & evidence

ORD record
ord-490d7022b12a46988a4e12144416bcef
Source dataset
uspto-grants-1998_12
Patent number
US05849736

Reaction notes

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