Sodium Hydroxide → Glpg-0974

HRID 408626Notes

Reaction equation

C[O:2][C:3](=[O:34])[CH2:4][CH2:5][CH2:6][N:7]([C:16]([C@@:18]1([CH3:33])[CH2:21][CH2:20][N:19]1[C:22]([C:24]1[C:25]2[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=2[S:27][CH:28]=1)=[O:23])=[O:17])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[CH:10]=1.[OH-].[Na+]>CO>[S:27]1[CH:28]=[C:24]([C:22]([N:19]2[CH2:20][CH2:21][C@:18]2([CH3:33])[C:16]([N:7]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[CH:10]=2)[CH2:6][CH2:5][CH2:4][C:3]([OH:34])=[O:2])=[O:17])=[O:23])[C:25]2[CH:32]=[CH:31][CH:30]=[CH:29][C:26]1=2

Participants

Conditions

Temperature: 20 °C

Procedure

To a solution of 4-[[(R)-1-(benzo[b]thiophene-3-carbonyl)-2-methyl-azetidine-2-carbonyl]-(3-chloro-benzyl)-amino]-butyric acid methyl ester, Intermediate 112 (25 g, 1 eq.) in 750 mL of MeOH was added aqueous NaOH (2N) (75 mL, 3 eq.). The reaction was stirred at 20° C. for 15 h. The solvent was removed under reduced pressure and the crude was partitioned between water and EtOAc. The organic layer was discarded. The aqueous layer was acidified by addition of HCl (2N) until pH=2 and thoroughly extracted three times with EtOAc. The organic layers were combined, dried over MgSO4, filtered and concentrated under reduced pressure to afford 4-[[(R)-1-(benzo[b]thiophene-3-carbonyl)-2-methyl-azetidine-2-carbonyl]-(3-chloro-benzyl)-amino]-butyric acid (23.7 g, yield=97%).

Workup

customThe solvent was removed under reduced pressure
customthe crude was partitioned between water and EtOAc
additionThe aqueous layer was acidified by addition of HCl (2N) until pH=2
extractionthoroughly extracted three times with EtOAc
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-3e7fbe8451e243f8ab8ca292f3528aed
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759334B2

Reaction notes

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