Benzyl chloroformate → Methyl 4-(4-(chloromethyl)-5-methyloxazol-2-yl)benzoate

HRID 1526849Notes

Reaction equation

BrC1C=CC(S(CC2N=[C:14]([C:18]3[CH:33]=[CH:32][C:21]([C:22]([NH:24][CH2:25][C:26]4[CH:27]=NC=CC=4)=O)=[CH:20][CH:19]=3)[O:15][C:16]=2C)(=O)=O)=CC=1.[Cl:34][C:35](OCC1C=CC=CC=1)=O.BrC1C=CC(S(CC2N=C(C3C=CC(C(O)=O)=CC=3)OC=2C)(=O)=[O:53])=CC=1.[OH-:71].[Na+]>C1COCC1>[Cl:34][CH2:35][C:25]1[N:24]=[C:22]([C:21]2[CH:20]=[CH:19][C:18]([C:14]([O:15][CH3:16])=[O:53])=[CH:33][CH:32]=2)[O:71][C:26]=1[CH3:27]

Participants

Conditions

Temperature: 20 °C

Procedure

4-(Benzyloxycarbonylamino)methyl)benzoic acid (30). Benzyl chloroformate (10.3 mL, 72.7 mmol) and 2 M NaOH solution (33 mL, 66 mmol) were simultaneously added dropwise to a stirred solution of 4-aminomethylbenzoic acid (29) (10.0 g, 66.2 mmol) in 2 M NaOH solution (33 mL) and THF (30 mL) at 0° C. The mixture was stirred at 20° C. for 16 h, then the organic solvent was evaporated and the residue acidified with 2 M HCl until the pH of the mixture was 2-3. The precipitate was filtered, washed with water (250 mL), washed with EtOH (50 mL), and finally washed with Et2O (100 mL). The solid was dried under vacuum to give acid 2 (16.43 g, 87%) as a white powder: mp 190-192° C. [lit. (Loge et. al., J. Enzyme Inhibit. Med. Chem. 2002, 17, 381-390) mp (toluene) 194-195° C.; 1H NMR δ 7.85 (br d, 2 H, H-2, H-6), 7.82 (br t, J=6.1Hz, 1 H, NHCO2), 7.30-7.40 (m, 5 H, H-2′, H-3′, H-4′, H-5′, H-6′), 7.27 (br d, J=8.2Hz, 2 H, H-3, H-5), 5.05 (s, 2H, OCH2), 4.24 (d, J=6.1Hz, 2 H, CH2N).

Workup

customthe organic solvent was evaporated
filtrationThe precipitate was filtered
washwashed with water (250 mL)
washwashed with EtOH (50 mL)
washfinally washed with Et2O (100 mL)
customThe solid was dried under vacuum

Sources & evidence

ORD record: ord-456a80b8769e406a8945f5de0c091096
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085570B2

Reaction notes

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