Potassium Hydroxide → (1R,3S,5S)-5-(Tetrahydro-pyran-2-yloxymethyl)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-tert-butyl ester

HRID 1527431Notes

Reaction equation

C([O:3][C:4]([C@@H:6]1[CH2:11][C@:10]2([CH2:12][O:13][CH:14]3[CH2:19][CH2:18][CH2:17][CH2:16][O:15]3)[C@@H:8]([CH2:9]2)[N:7]1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:5])C.[OH-].[K+]>CO.C1COCC1.O.CCOC(C)=O>[C:23]([O:22][C:20]([N:7]1[C@H:6]([C:4]([OH:5])=[O:3])[CH2:11][C@:10]2([CH2:12][O:13][CH:14]3[CH2:19][CH2:18][CH2:17][CH2:16][O:15]3)[C@H:8]1[CH2:9]2)=[O:21])([CH3:26])([CH3:24])[CH3:25]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of (1R,3S,5S)-5-(tetrahydro-pyran-2-yloxymethyl)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-tert-butyl ester 3-ethyl ester (510 mg, 1.38 mmol) in MeOH (2.3 mL), THF (2.3 mL) and water (2.3 mL) was added KOH (155 mg, 2.76 mmol). The reaction was stirred at 60° C. for 45 min. Then allowed to cool to RT and diluted with EtOAc. The layers were separated, the aqueous layer was acidified by addition of HCl (0.1N, until pH 1) and extracted with EtOAc (×2). The organics were dried (Na2SO4), filtered and concentrated. MS (UPLC/MS): 359.4 [M+NH4]+, 340.4 [M−H]−, 386.4 [M+HCOO]−, 681.5 [2M−H]−; tR (HPLC conditions f): 1.84 min.

Workup

temperatureto cool to RT
customThe layers were separated
additionthe aqueous layer was acidified by addition of HCl (0.1N, until pH 1)
extractionextracted with EtOAc (×2)
dry with materialThe organics were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated
custom1.84 min.

Sources & evidence

ORD record: ord-b689de084e9f43d89c3a1d1a7247940a
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085555B2

Reaction notes

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