4-Methylmorpholine → methyl (5R)-1-{(2S)-2-((tert-butoxycarbonyl)amino)-2-cyclopentylethanoyl}-5-((trimethylsilyl)ethynyl)-L-prolinate

HRID 475339

Reaction equation

HRID 475339 reaction equation
[CH3:1][Si:2]([C:5]#[C:6][C@@H:7]1[NH:11][C@H:10]([C:12]([O:14][CH3:15])=[O:13])[CH2:9][CH2:8]1)([CH3:4])[CH3:3].CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.C1(NC2CCCCC2)CCCCC1.[C:48]([O:52][C:53]([NH:55][C@@H:56]([CH:60]1[CH2:64][CH2:63][CH2:62][CH2:61]1)[C:57](O)=[O:58])=[O:54])([CH3:51])([CH3:50])[CH3:49]>ClCCl.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[C:48]([O:52][C:53]([NH:55][C@@H:56]([CH:60]1[CH2:61][CH2:62][CH2:63][CH2:64]1)[C:57]([N:11]1[C@@H:7]([C:6]#[C:5][Si:2]([CH3:3])([CH3:4])[CH3:1])[CH2:8][CH2:9][C@H:10]1[C:12]([O:14][CH3:15])=[O:13])=[O:58])=[O:54])([CH3:51])([CH3:49])[CH3:50]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 16090847methyl (5R)-5-((trimethylsilyl)ethynyl)-L-prolinateHCID 46737275Boc-Cyclopentyl-Gly-OH DCHA

Product 1

HCID 66756897methyl (5R)-1-{(2S)-2-((tert-butoxycarbonyl)amino)-2-cyclopentylethanoyl}-5-((trimethylsilyl)ethynyl)-L-prolinate

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of methyl (5R)-5-((trimethylsilyl)ethynyl)-L-prolinate (1.2 g, 5.32 mmol) in dichloromethane (30 mL) at ambient temperature under nitrogen was added 4-dimethylamino pyridine (0.65 g, 5.32 mmol), 4-methylmorpholine (0.9 mL, 7.98 mmol), 1-(3-(dimethylamino)propyl)-3-ethyl carbodiimide hydrochloride (1.22 g, 6.39 mmol), and (2S)-((tert-butoxycarbonyl)amino)(cyclopentyl)acetic acid dicyclohexylamine salt (1.55 g, 6.39 mmol). The reaction mixture was stirred at room temperature for 16 hours, diluted with ethyl acetate and washed with 1 M HCl. The aqueous layer was further extracted with ethyl acetate (2×) and the combined ethyl acetate layers were dried (Na2SO4) and evaporated. The residue was purified by flash chromatography 30% ethyl acetate/hexane to provide the titled compound. MS (CI) m/e 451 (M+H)+.

Workup

  1. washwashed with 1 M HCl
  2. extractionThe aqueous layer was further extracted with ethyl acetate (2×)
  3. dry with materialthe combined ethyl acetate layers were dried (Na2SO4)
  4. customevaporated
  5. customThe residue was purified by flash chromatography 30% ethyl acetate/hexane

Sources & evidence

ORD record
ord-ee85dbebbbfc471bacd064c749de9f34
Source dataset
uspto-grants-2014_01
Patent number
US08637546B2

Linked notes

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