4-Methylmorpholine → HCID 13685983, compound

HRID 1980763Notes

Reaction equation

[F:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][O:7][C:8]([N:10]2[CH2:17][CH2:16][CH2:15][C@H:11]2[C:12]([OH:14])=O)=[O:9])=[CH:4][CH:3]=1.ClC(OCC(C)C)=O.CN1CCOCC1.[NH2:35][C@H:36]([CH2:40][OH:41])[CH:37]([CH3:39])[CH3:38]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][O:7][C:8]([N:10]2[CH2:17][CH2:16][CH2:15][C@H:11]2[C:12]([NH:35][C@H:36]([CH2:40][OH:41])[CH:37]([CH3:39])[CH3:38])=[O:14])=[O:9])=[CH:18][CH:19]=1

Participants

Reactant 4

HCID 79724-Methylmorpholine

HCID 62365Isobutyl chloroformate

HCID 640993L-Valinol

HCID 13685981HCID 13685981, compound

Product 1

HCID 13685983HCID 13685983, compoundYield 78.7%

Procedure

N-(4-fluorobenzyloxycarbonyl)-L-prolyl-L-valinol was prepared from 16.1 g (60.2 mmol) p-fluorobenzyloxycarbonyl-L-proline, 8.22 g (60.2 mmol) isobutyl chloroformate, 6.09 g (60.2 mmol) N-methylmorpholine, and 6.21 g (60.2 mmol) L-valinol, substantially according to the mixed anhydride procedure described in Example 1. The resulting crude product (19.46 g) was recrystallized from a mixture of 100 mL ethyl acetate and 200 mL n-hexane to give 16.69 g (47.4 mmol, 78.7%) of N-(4-fluorobenzyloxycarbonyl)-L-prolyl-L-valinol, m.p. 123°-124°. αD25 -60.2° (C=1.02 g/100 mL in acetone). An nmr obtained for this material spectrum verified the assigned structure: 1H NMR (CDCl3 /TMSi), 220 mc, δ0.85, m, 6H (valinol CH3); δ1.9, m, 2H (proline γ-CH2); δ2.2, m, 3H (valinol β-CH and proline β-CH2); δ 3.35, m, 3H (proline δCH2); δ 3.58, m, 2H (CH2OH); δ 4.34, m, H (valinol α-CH); δ 5.0, s, 2H (benzyl CH2); δ 6.30-6.80, m, H (NH); δ 7.03, m, 2H (aromatic); δ 7.35, m, 2H (aromatic).

Workup

customThe resulting crude product (19.46 g) was recrystallized from a mixture of 100 mL ethyl acetate and 200 mL n-hexane

Sources & evidence

ORD record: ord-8492ec415ad341ed82ea2a12c6506354
Source dataset: uspto-grants-1985_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04511390

Reaction notes

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