Trifluoroacetic acid → 8-[4-({(2S,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)benzoyl]-2-oxa-8-azaspiro[4.5]decan-1-one

HRID 1804649Notes

Reaction equation

HRID 1804649 reaction equation
[OH:1][C@H:2]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C@H:3]1[CH2:7][CH2:6][C@@H:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([N:17]3[CH2:27][CH2:26][C:20]4([C:24](=[O:25])[O:23][CH2:22][CH2:21]4)[CH2:19][CH2:18]3)=[O:16])=[CH:11][CH:10]=2)[N:4]1C(OC(C)(C)C)=O.FC(F)(F)C(O)=O>ClCCl>[OH:1][C@H:2]([C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)[C@@H:3]1[NH:4][C@H:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([N:17]3[CH2:18][CH2:19][C:20]4([C:24](=[O:25])[O:23][CH2:22][CH2:21]4)[CH2:26][CH2:27]3)=[O:16])=[CH:11][CH:10]=2)[CH2:6][CH2:7]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86666757tert-butyl (2R,5S)-2-[(R)-hydroxy(phenyl)methyl]-5-{4-[(1-oxo-2-oxa-8-azaspiro[4.5]dec-8-yl)carbonyl]benzyl)pyrrolidine-1-carboxylate

Product 1

HCID 679721068-[4-({(2S,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)benzoyl]-2-oxa-8-azaspiro[4.5]decan-1-oneYield 80.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 28 mg (0.05 mmol) of the title compound from Step A above in 1 ml anhydrous dichloromethane at ambient temperature was added 0.3 ml trifluoroacetic acid. The solution was stirred for 1 h. It was then evaporated and purified by reverse-phase HPLC (TMC Pro-Pac C18; 5-65% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient). The pure fractions were lyophilized overnight to give 18 mg (80%) of the title compound as a white solid. LC/MS 449.2 (M+1). 1H NMR (DMSO): δ 7.27-7.32 (m, 8H), 7.19-7.22 (m, 1H), δ 5.15 (bs, 1H), δ 4.28 (t, J=6.8 Hz, 2H), δ 4.23 (d, J=7.2 Hz, 1H), δ 4.20 (bs, 1H), δ 3.60 (bs, 1H), δ 3.27 (t, J=7.0 Hz, 1H), δ 3.21 (m, 2H), δ 3.11 (q, J=7.1 Hz, 1H), δ 2.71 (qd, J=13.1, 6.8 Hz, 2H), δ 2.23 (s, 2H), δ 1.52-1.65 (m, 5H), δ 1.38-1.44 (m, 1H), δ 1.28-1.34 (m, 2H).

Workup

  1. customIt was then evaporated
  2. custompurified by reverse-phase HPLC (TMC Pro-Pac C18; 5-65% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient)
  3. waitThe pure fractions were lyophilized overnight

Sources & evidence

ORD record
ord-e589fad15ebe45caa6fbb2df958b7916
Source dataset
uspto-grants-2013_01
Patent number
US08354403B2

Reaction notes

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