Triethylamine → 8-((2S)-2-(benzyloxycarbonylamino)-4-(methylthio)butanamido)-1,4-dioxaspiro[4.5]decane

HRID 1374279Notes

Reaction equation

HRID 1374279 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([NH2:11])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[C:12]([NH:22][C@H:23]([C:28](O)=[O:29])[CH2:24][CH2:25][S:26][CH3:27])([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C>C(Cl)Cl>[CH2:15]([O:14][C:12]([NH:22][C@@H:23]([CH2:24][CH2:25][S:26][CH3:27])[C:28]([NH:11][CH:8]1[CH2:9][CH2:10][C:5]2([O:4][CH2:3][CH2:2][O:1]2)[CH2:6][CH2:7]1)=[O:29])=[O:13])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 1550857Benzyloxycarbonyl-L-methionineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 146343151,4-Dioxaspiro[4.5]decan-8-amine

Product 1

HCID 210751288-((2S)-2-(benzyloxycarbonylamino)-4-(methylthio)butanamido)-1,4-dioxaspiro[4.5]decaneYield 64.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1,4-Dioxaspiro[4.5]decan-8-amine (5.03 g, 32.0 mmol, 1 eq.), CBZ-L-methionine (10.90, 38.4 mmol, 1.2 eq.), 1-hydroxybenzotriazole hydrate (HOBT) (5.19 g, 38.4 mmol, 1.2 eq.), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide HCl (EDCI) (7.36 g, 38.4 mmol, 1.2 eq.), triethylamine (8.92 mL, 64.0 mmol, 2 eq.) and methylene chloride (150 mL) were stirred at room temperature under nitrogen for 72 hours. Worked up by rinsing 3 times with saturated sodium bicarbonate (50 mL). The organic layer was dried over sodium sulfate and stripped to give an amber oil which solidified. The solids were triturated with diethyl ether (100 mL) and stirred overnight. The solids were filtered to give 8-((2S)-2-(benzyloxycarbonylamino)-4-(methylthio)butanamido)-1,4-dioxaspiro[4.5]decane (8.75 g) as a white solid. Yield=64%. Mass Spec (ESI) detects (M+H)+=423.22.

Workup

  1. washby rinsing 3 times with saturated sodium bicarbonate (50 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. customto give an amber oil which
  4. customThe solids were triturated with diethyl ether (100 mL)
  5. filtrationThe solids were filtered

Sources & evidence

ORD record
ord-b6053518fa0f4257a54a6fa3f9b15c96
Source dataset
uspto-grants-2007_01
Patent number
US07163937B2

Reaction notes

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