Hydrochloric Acid → Diisopropyl Ether

HRID 2412322Notes

Reaction equation

HRID 2412322 reaction equation
[NH:1]1[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3](O)=[O:4].C[N:10]1[CH2:15][CH2:14][O:13]CC1.[CH2:16]([O:18]C(Cl)=O)[CH3:17].Cl.[NH2:23][C@H:24]([C:35]([NH:37][C@H:38]([C:43]([NH2:45])=[O:44])[CH2:39][CH2:40][S:41][CH3:42])=[O:36])[CH2:25][C:26]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[NH:28][CH:27]=1.[O:46]1C[CH2:49][CH2:48][CH2:47]1>CN(C)C=O>[NH:10]1[C:47](=[O:46])[CH2:48][CH2:49][C@H:17]1[C:16]([N:1]1[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([NH:23][C@H:24]([C:35]([NH:37][C@H:38]([C:43]([NH2:45])=[O:44])[CH2:39][CH2:40][S:41][CH3:42])=[O:36])[CH2:25][C:26]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[NH:28][CH:27]=1)=[O:4])=[O:18].[CH:14]([O:13][CH:7]([CH3:6])[CH3:8])([CH3:15])[CH3:16]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-Methylmorpholine2×HCID 8028TetrahydrofuranHCID 10928Ethyl chloroformateHCID 145742L-ProlineHCID 13306579HCID 13306579, compound

Product 2

HCID 7914Diisopropyl EtherHCID 13306581HCID 13306581, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1.584 g (7 mmol) of Pry-Pro-OH (III) dissolved in 20 ml of anhydrous tetrahydrofuran, 0.79 ml (7 mmol) of N-methylmorpholine and 0.69 ml (7 mmol) of ethylchloroformate were successively added at -12° C. After stirring for 2 minutes, a cold solution of 2.596 g (7 mmol) of HCl.H-Trp-Met-NH2 (II) and 0.79 ml (7 mmol) of N-methylmorpholine in 20 ml of dimethylformamide was added. The reaction mixture was stirred for 1 h at -12° C. and for 2 h at 0°-15° C., then filtered to remove salts and evaporated in vacuo. The crude product was purified by column chromatography on silica gel (Merck) 0.040-0.063 mm with an eluent of chloroform:methanol:water of 87:13:1 by volume. A 2.545 g (67% yield) amount of IV was obtained from diisopropyl ether: m.p. 207°-209° C., [α]D23 = -95.3° (c=1 MeOH); RfC 0.43. Amino acid ratio: Glu 1.00; Pro 0.98; Met 1.00.

Workup

  1. stirringThe reaction mixture was stirred for 1 h at -12° C. and for 2 h at 0°-15° C.
  2. filtrationfiltered
  3. customto remove salts
  4. customevaporated in vacuo
  5. customThe crude product was purified by column chromatography on silica gel (Merck) 0.040-0.063 mm with an eluent of chloroform

Sources & evidence

ORD record
ord-67fca4155c364d61969f29b074e84c80
Source dataset
uspto-grants-1985_01
Patent number
US04491541

Reaction notes

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