Sodium Hydroxide → HCID 68283741, compound

HRID 1527424Notes

Reaction equation

HRID 1527424 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:13]([C:14](=[O:25])[NH:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=2[F:24])[CH2:12][C@@:11]2([CH2:26][OH:27])[C@@H:9]1[CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:28](OC([C@@H]1C[C@@]2(COC)[C@H](C2)N1C(OC(C)(C)C)=O)=O)C.[OH-].[Na+].O[Li].O>>[C:1]([O:5][C:6]([N:8]1[C@H:13]([C:14](=[O:25])[NH:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=2[F:24])[CH2:12][C@@:11]2([CH2:26][O:27][CH3:28])[C@@H:9]1[CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 4

HCID 14798Sodium HydroxideHCID 168937Lithium hydroxide, monohydrateHCID 68283128HCID 68283128, compoundHCID 68283760HCID 68283760, compound

Product 1

HCID 68283741HCID 68283741, compound

Procedure

were obtained using the same protocols as described in Scheme B28 steps D and E for the preparation of (1R,3S,5S) and (1S,3S,5R)-3-(3-chloro-2-fluoro-benzylcarbamoyl)-5-hydroxymethyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester starting from (1R,3S,5S) and (1S,3S,5R)-5-methoxymethyl-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-tert-butyl ester 3-ethyl ester. NaOH was replaced by LiOH.H2O in step D. The diastereoisomers were separated by flash column chromatography on silica gel (c-hexane/EtOAc 1:1 to EtOAc) to give (1S,3S,5R)-3-(3-chloro-2-fluoro-benzylcarbamoyl)-5-methoxymethyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester as a colorless oil: TLC, Rf (c-hexane/EtOAc 1:1)=0.50; MS (UPLC/MS): 413.3/415.2 [M+H]+, 457.3/459.3 [M+HCOO]−; tR (HPLC conditions a): 3.74 min and (1R,3S,5S)-3-(3-chloro-2-fluoro-benzylcarbamoyl)-5-methoxymethyl-2-aza-bicyclo[3.1.0]hexane-2-carboxylic acid tert-butyl ester as a colorless oil: TLC, Rf (c-hexane/EtOAc 1:1)=0.30; MS (UPLC/MS): 413.2/415.3 [M+H]+, 457.3/459.3 [M+HCOO]−; tR (HPLC conditions a): 3.57 min.

Workup

  1. customwere obtained
  2. customThe diastereoisomers were separated by flash column chromatography on silica gel (c-hexane/EtOAc 1:1 to EtOAc)

Sources & evidence

ORD record
ord-d6a51de8895248ecbf02a11e4cc1a2f1
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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